Tumors are major diseases plaguing human health, and immunotherapy for tumors has become the fourth category of anti-tumor therapies that have been proven to have significant clinical therapeutic effects and advantages after surgery, radiotherapy and chemotherapy. Due to the high complexity, diversity and variability of biological characteristics of tumors, it has become a great challenge for scientists to understand the mechanisms of tumor development and find therapeutic methods for tumors. From the first tumor vaccine based on bacterial products designed by Coley in the 1890s, to the exploration of antibody therapy and cytokine therapies in the 1970s and 1980s, to the immunotherapy methods such as tumor vaccines and cellular immunity approved for some specific cancers one after another a few years ago, immunotherapy for tumors has experienced more than 100 years of development and progress. TNF, the earliest and most representative drug in tumor immunotherapy, was first discovered in 1975, and is mainly produced by activated macrophages, NK cells and T lymphocytes. Although TNF-α and TNF-β have only about 30% homology, they share a common receptor. TNF acts on vascular endothelial cells, damaging endothelial cells or causing vascular dysfunction, causing vascular damage and thrombosis, resulting in bleeding, hypoxic necrosis due to local blood flow blockage in tumor tissues.4. Improves phagocytosis of neutrophils, increases peroxide anion production, enhances ADCC function, and stimulates cellular decompensation. Enhance ADCC function, stimulate cell degranulation and secretion of myeloperoxidase.5. Promote cell proliferation and differentiation: TNF promotes T cell MHC class I antigen expression, enhances IL-2-dependent thymocyte and T cell proliferation, promotes differential lymphokine production such as IL-2, CSF and IFN-γ, and enhances mitogen or foreign antigen-stimulated B cell proliferation and Ig secretion. Numerous basic studies have demonstrated that tumor necrosis factor can enhance the concentration of chemotherapeutic agents in tumors 4-6 times; combining with adriamycin improves the cytotoxic effect of multidrug-resistant cells; combining with cisplatin, paclitaxel and gemcitabine has a synergistic effect. At the 35th ASCO (American Society of Clinical Oncology) annual meeting in 1995, experts reached a consensus: (1) TNF has significant efficacy in tumor treatment. (2) TNF is a promising antitumor drug, and more support should be given to research and treatment of TNF in the future. Meanwhile, the European Medicines Evaluation Committee (EMEA) has also registered and accepted TNF as an antitumor drug. In addition, the US FDA approved the phase III clinical study protocol of TNF for metastatic melanoma led by the National Cancer Institute (NCI). In particular, at the end of the 20th century, several European clinical studies applied tumor necrosis factor to isolated limb end perfusion in soft tissue sarcoma and malignant melanoma to obtain sensational results with efficiency rates as high as 70-90%, such satisfactory results are rare in the history of tumor biotherapy. The clinical study conducted in Germany also explored the use of tumor necrosis factor alone in the treatment of advanced refractory recurrent malignant thoracic ascites, and the results showed that the efficiency of tumor necrosis factor in the treatment of cancerous thoracic ascites was as high as 87%, and the efficiency for recurrent refractory thoracic ascites was still as high as 86% with mild adverse effects, which is the most effective drug for the treatment of malignant thoracic ascites. A large number of clinical studies have confirmed that tumor necrosis factor has unique advantages in the treatment of malignant thoracoabdominal water, which is consistent with the reports from abroad. In solid tumors, tumor necrosis factor combined with chemotherapy can significantly improve the chemotherapeutic efficacy of advanced NSCLC and NHL. As the research progresses, the clinical application of tumor necrosis factor will be more promising. Especially in recent years, with the deepening understanding of the relationship between tumor and host, especially the body’s anti-tumor immune response and tumor immune escape mechanism, we believe that the application of combined interventions based on immune cells, molecules and genes in tumor treatment will become a major hot spot for basic and clinical scientists to focus on, and will benefit more cancer patients in clinical application.