Liver cancer is one of the common malignant tumors in clinic, and the incidence rate has been increasing year by year. Most patients are diagnosed at the advanced stage, and the prognosis is poor. The occurrence and development of hepatocellular carcinoma is closely associated with immune elimination, balance and escape. In recent years, checkpoint inhibitors have been used in clinic and immune checkpoint inhibitors have made extensive progress and application in clinical research, which has brought a significant opportunity to improve the survival rate of patients with advanced liver cancer. However, HCC patients develop immunotherapy resistance afterwords. The poor drug response to tumor cells is a serious problem affecting the clinical prognosis. This review briefly summarizes the potential mechanism of innate resistance and acquired resistance in immunotherapy of liver cancer.