Primary liver cancer, mainly hepatocellular carcinoma, is a common malignancy worldwide. According to global statistics in 2018, the incidence of liver cancer was 854,000/year and the death rate was 810,000/year. East Asia and Africa are the high incidence areas of liver cancer, especially China, Japan, and Korea. In China, liver cancer is known as the “king of cancers”. The latest edition of CSCO guidelines for the treatment of advanced hepatocellular carcinoma states that for patients with good liver function (Child-Pugh score ≤7), the recommended first-line treatment is sorafenib or lenvatinib, and Oxaliplatin-based systemic chemotherapy; in the second-line treatment choice, regorafenib, PD-1 monoclonal antibody (including nabritumomab and pabrolizumab) as Class I recommendation. In addition to the domestic CSCO guidelines, several authoritative foreign guidelines such as NCCN, ESAL, ESMO guidelines have recommended PD-1 as the representative immune checkpoint inhibitor as the second-line treatment for advanced hepatocellular carcinoma. First, we interpret the rationale of PD-1 antibody for advanced hepatocellular carcinoma. From the perspective of immunology, the liver is a very special organ, and the food and protein we eat every day need to be metabolized by the liver, so the liver has a strong immune tolerance function. The special population of cells in the liver that suppress immune response makes the liver an immune immune immune immune organ. However, for tumor patients, in the liver microenvironment, these immunosuppressive cells help tumor cells evade killing by the body’s T lymphocytes, leading to tumor immune escape and progressive metastasis. Immune checkpoint inhibitors (PD-1/PD-L1 antibodies) can promote the activation and proliferation of T cells in the tumor microenvironment, restore the activity of killer T lymphocytes, and achieve the effect of killing cancer cells. Immunotherapeutic drugs represented by PD-1 antibodies have been approved in more than 60 regions, including the United States, the European Union and Japan, for the treatment of lung cancer, melanoma, bladder cancer, lymphoma, liver cancer and many other cancer types. How effective is PD-1 in treating advanced liver cancer? From the results of Check-Mate040, an international multicenter phase II single-arm clinical study, the tumor remission rate of advanced hepatocellular carcinoma treated with navulizumab ranged from 14% to 23% (tumor remission rate refers to tumor shrinkage or disappearance), the disease control rate of those who did not receive sorafenib was 54%, and those who received sorafenib was 55% (disease control rate refers to tumor stabilization, shrinkage or disappearance after treatment (disease control rate refers to the percentage of the treated population whose tumors are stable, shrinking or disappearing). In terms of survival benefit, patients who did not receive sorafenib had a survival of 28.6 months, which is encouraging since we all know that the 2-year survival rate for advanced liver cancer is very low, and patients who received sorafenib had a survival of about 15 months, which is also very good. Are all liver cancer patients treated with PD-1 effective? In fact, there are still many patients who do not respond to immune checkpoint inhibitors. In terms of objective tumor remission rates, about 20% of patients with liver cancer will experience tumor shrinkage or even disappearance with PD-1 antibodies, but there are still many patients who experience tumor progression after PD-1 treatment. Therefore, immunotherapy strategies for hepatocellular carcinoma still need to be improved, and many clinical studies to improve the efficacy of immunotherapy are underway. Is there any difference in the efficacy of domestically produced PD-1 antibodies and imported PD-1 antibodies? Currently, PD-1 antibodies available in China include imported nabolutumab (O drug) and pablizumab (K drug). There are also more types of domestic PD-1 antibodies, including carrilizumab, teraplizumab, sindilizumab, etc. Domestic PD-1 antibodies have a significant price advantage over imported PD-1 antibodies. As for the efficacy, no clinical studies have been conducted to compare the efficacy of various PD-1 antibodies, so there is no data to confirm the efficacy of imported PD-1 antibodies over domestic PD-1 antibodies. In clinical studies of PD-1 antibody-related liver cancer, the objective remission rate of imported or domestic PD-1 antibodies for liver cancer was around 13%-20%, with no significant difference. If patients have poor treatment efficacy with domestic PD-1 antibodies, it is not recommended that they switch to imported PD-1 to improve treatment efficacy. What are the adverse effects of PD-1 antibodies for hepatocellular carcinoma? From the existing clinical experience, the application of PD-1 antibodies for hepatocellular carcinoma is relatively safe, and the probability of serious side effects is low (<10%). Among them, skin toxicity is the most common, and some patients may have abnormal thyroid function (hyper- or hypothyroidism), autoimmune enteritis with diarrhea, autoimmune hepatitis, autoimmune pneumonia, autoimmune pancreatitis, pituitary inflammation, etc. In addition, very few patients may develop autoimmune pancreatitis. In addition, a very small number of patients develop autoimmune myocarditis, which can be life-threatening. There is no way to predict clinically which patients will experience serious adverse reactions with PD-1. Therefore, when using this drug, patients with hepatocellular carcinoma need to pay attention to the adverse drug reactions that occur in themselves and regularly follow up the blood routine, liver function, thyroid function, cardiac enzymes and related hormone levels, and if there are any abnormalities, go to the hospital for treatment in time to avoid serious adverse reactions. What are the methods to improve the efficacy of immunotherapy for liver cancer? It can be said that the current liver cancer treatment has entered a new era of immunotherapy. However, it is undeniable that the efficacy of immune checkpoint inhibitors in the treatment of liver cancer is still limited. Clinical studies in the past 2 years have confirmed that the combination of molecular targeted therapy and immune checkpoint inhibitors can increase the efficiency of immunotherapy to more than 30%. Currently, the combination regimens that have proven effective in clinical trials include lenvatinib in combination with pablizumab, anvitin in combination with atelelizumab, and apatinib in combination with karelizumab. The combination of local ablation, chemotherapy, radiotherapy and immunotherapy has also been gradually carried out in the clinic. It is reasonable to believe that the comprehensive treatment model of liver cancer with immunotherapy as the core will bring gospel to more patients with advanced liver cancer.