In the past 10 years, the progress in systemic therapy for hepatocellular carcinoma (HCC) is attributed to the application of molecular target therapy and the improvement in immunotherapy. The immunosuppressive microenvironment of HCC enables HCC cells to avoid attack by the immune system, which is also an important reason for the progression of HCC. Improving immune killing of HCC and correcting immunosuppressive conditions are important strategies for immunotherapy for HCC. Tumor vaccine therapy based on HCC specific antigen, genetically engineered T lymphocytes, and basic research and bench-to-bedside translation of immune checkpoint inhibitors have significantly improved the outcome of immunotherapy. Further studies should be performed for immunotherapy combined with other antitumor therapies such as local ablation, molecular targeted therapy, and tumor vaccine therapy.