ObjectiveTo systematically summarize recent research advances in immunotherapy for hepatocellular carcinoma (HCC) and analyze key challenges in this field. MethodsThrough a systematic review of literature, this study concludes researches on the application of immune checkpoint inhibitors in HCC treatment, combination therapy strategies, and mechanisms of drug resistance. ResultsImmune therapies, particularly immune checkpoint inhibitors, have significantly transformed the treatment landscape of hepatocellular carcinoma. Dual immune combination therapies and immunotherapies combined with anti-angiogenic agents have become new treatment strategies. However, high heterogeneity of HCC, complex tumor microenvironment and the resulting acquired drug resistance remain major which affect the efficacy of immunotherapy. ConclusionAlthough immunotherapy bring new hope in HCC patients, further in-depth investigation on resistance mechanisms and develop novel combination treatment strategies are needed to break through the bottleneck of current immunotherapy.