Abstract: Immunotherapy is considered as the fourth cancer treatment after surgery, radiotherapy and chemotherapy. With the in-depth research on immunotherapy in recent years, especially immuno-checkpoint inhibitors, PD-1/PD-L1 pathway inhibitors have been approved for the treatment of many cancer species. But due to the immune response of tumor cells through multiple drug-resistant mechanisms, immuno-checkpoint blockade has some problems, such as low overall response rate, primary or secondary drug resistance and so on. This paper expounds the mechanism of tumor immune resistance and explores strategies for further treatment after drug resistance, which provides a new theoretical and clinical basis for improving the response rate of immune checkpoint inhibitors and reducing the probability of immune resistance.