1. Overview of liver transplantation for liver cancer Primary liver cancer includes hepatocellular liver cancer, cholangiocellular carcinoma and mixed cell carcinoma of both. The incidence rate of primary liver cancer in China reaches 80/1 million, because most of the patients are in the middle and late stage when they are diagnosed, and more than 80% of them are combined with cirrhosis, the actual surgical resection rate is <30%, and the postoperative recurrence rate is >70%. Liver transplantation has been declared by the World Health Organization (WHO) as the only effective treatment for various end-stage liver diseases. As a more effective means of treating liver cancer, liver transplantation has the characteristics of completely curing the tumor and curing cirrhosis at the same time, and has the incomparable advantages of traditional liver resection in the surgical treatment of liver cancer. However, postoperative tumor recurrence and metastasis affect the efficacy of liver transplantation in the treatment of liver cancer and restrict the development of liver transplantation in the treatment of liver cancer. Therefore, how to select reasonable cases to reduce tumor recurrence after liver transplantation has become an urgent problem in liver transplantation clinics in China. And because of the poor results of liver transplantation for cholangiocellular carcinoma and high recurrence rate after surgery, liver transplantation is not recommended at present. For the selection of liver transplantation indications for hepatocellular carcinoma, the Milan criteria (single tumor diameter <5cm; or no more than 3 tumors, each tumor diameter <3cm; no vascular invasion and lymph node metastasis) have been adopted by most transplantation centers, and its 5-year survival rate is over 70%. In 1998, the National Organ Collaborative Network (UNOS) officially established it as a selection criterion for liver cancer transplant patients. However, its overly stringent nature has resulted in many patients with hepatocellular liver cancer being denied transplantation opportunities. Therefore, new criteria are constantly being introduced. 2. Prevention of tumor recurrence after liver transplantation for hepatocellular carcinoma 2.1. Preoperative prevention Selecting the appropriate indication is the most important factor in preventing recurrence of liver cancer after liver transplantation. For patients with liver cancer who have been included in the waiting list for transplantation, waiting too long for liver donation may increase the chance of tumor recurrence after transplantation due to tumor growth. Thus, for patients with an estimated waiting time of more than 1 month, the following treatment options are available to control tumor development: hepatic artery chemoembolization (TACE) is the conventional preferred method of non-surgical treatment for patients with hepatocellular carcinoma; anhydrous alcohol injection (PEI) is suitable for patients with tumors ≤3 cm and the number of tumors ≤3; radiofrequency ablation (RFA) is suitable for patients with tumors ≤5 cm; argon helium knife treatment is suitable for patients with tumors patients with ≤5cm. 2.2. Intraoperative prevention The operation and treatment during surgery have a significant influence on the tumor recurrence after surgery. Tumor metastasis and dissemination caused by surgical operation should be avoided as much as possible during surgery. In terms of surgery, the classical in situ liver transplantation is recommended, which helps complete resection of vena cava and retroperitoneal lymphatic tissue. It also requires strict adherence to the principle of anaplasia. Intraoperative intravenous mitomycin (MMC), 5-fluorouracil (5-Fu), or epirubicin (E-ADM) may be beneficial in reducing postoperative recurrence. In addition, intraoperative methylprednisolone dosage can be reduced to 500 mg. 2.3. Postoperative prophylaxis In addition to the routine postoperative management of liver transplantation, special attention should be paid to the use of immunosuppressive agents and postoperative chemotherapy. The main immunosuppressive agents are: tacrolimus (FK506), cyclosporine (CsA), morte-macrolimus (MMF), and corticosteroids (hormones, which need to be gradually reduced and discontinued as soon as possible). The postoperative regimen is a triple combination of FK506 or CsA + MMF + Pred, with early discontinuation of MMF and Pred. Some centers have tried to replace FK506 or CsA with rapamycin. Although there are reports in the literature that rapamycin and MMF have certain anti-tumor effects, the long-term use of immunosuppressants makes the overall decrease of the body's immunity and the weakening of tumor surveillance and inhibition, making the tumor easy to recur and grow. The occurrence of hepatocellular carcinoma in this foreigner is mostly related to hepatitis B virus infection, and the insufficient measures to prevent hepatitis B recurrence after transplantation are also the basis of tumor recurrence. Postoperative chemotherapy has the effect of inhibiting and removing possible residual tumor cells in the body, and is recommended for patients who exceed the Milan criteria, have vascular invasion or microscopic cancer emboli. The following postoperative chemotherapy regimens are available for reference: FMC regimen (5-Fu, 300 mg/m2, IV on days 1 and 4; MMC, 10 mg/m2, IV on days 2 and 5; carboplatin, 200 mg/m2, IV on days 3 and 6); FEM regimen (5-Fu, 300 mg/m2, IV on days 1 to 5; E-ADM, 70 mg/m2, IV on days 1 and 8 MMC, 10 mg/m2, day 1;) FOLFOX regimen (oxaliplatin, 150-200 mg, day 1 IV; calcium folinic acid, 0.2-0.3 g, day 1 IV; 5-FU, 2.5-3.0 g, micro-pump maintenance for 32-48 hours). 3.Treatment of recurrence after liver transplantation for hepatocellular carcinoma Regular postoperative (once a month in early stage, once every three months in long term, and can be extended appropriately after two years) examination of AFP, liver function, B ultrasound, CT, chest X-ray, bone scan, etc. is crucial for early diagnosis of postoperative tumor recurrence and improving the efficacy of postoperative recurrence. 3.1. Treatment of intrahepatic recurrence Recurrent tumor is located in one lobe of liver, especially for single tumor and no other contraindications, recurrent hepatectomy can be chosen. RFA and Ar-He knife are suitable for recurrent tumors ≤5cm. 3.2. Treatment of distant metastases of liver cancer 3.2.1. Lung metastases: Lobectomy can be considered for those with limited tumor and no contraindications; radiotherapy can be considered for inoperable lung metastases; oral chemotherapy with Herodal may be useful for some patients to relieve tumor development; RFA and Ar-He knife may be effective for tumor ≤5cm. 3.2.2. Bone metastasis: local radiotherapy and zoledronic acid can be used. 3.2.3. Systemic multi-organ metastasis: systemic chemotherapy can be used in addition to the above treatment. 4.Targeted therapy It is worth mentioning that the progress of molecular targeted therapy in advanced hepatocellular carcinoma is encouraging, the most notable of which is the multi-targeted drug sorafenib, which can effectively inhibit the formation of tumor neovascularization. Clinical studies have shown that sorafenib monotherapy ( 400 mg twice daily) in patients with advanced hepatocellular carcinoma resulted in a partial remission rate of 2.2%, a mild remission rate of 5.8%, stable disease for ≥16 weeks in 33.6% of patients, and a median disease progression-free time of 4.2 months. Another molecularly targeted drug is a recombinant humanized anti-VEGF monoclonal antibody, bevacizumab, which has been shown to have a remission rate of 20%, tumor stability of 27%, and median disease progression-free time of 5.3 months when given in combination with gemcitabine and oxaliplatin. However, most of the above strategies for the prevention and treatment of tumor recurrence after liver transplantation for hepatocellular carcinoma are based on retrospective clinical analyses that are not very reliable and are yet to be confirmed by well-designed prospective multicenter randomized controlled clinical trials. Only through continuous in-depth basic and clinical research and practice can we truly treat postoperative recurrence of hepatocellular carcinoma and systemic malignancies.