BACKGROUND: Treatment of hepatocellular carcinoma (HCC) is challenging as most patients are diagnosed at advanced stage with underlying chronic liver conditions. Conventional systemic chemotherapy has failed in HCC, and the clinical efficacy of FDA-approved molecular targeted agents such as sorafenib and lenvatinib remains unsatisfactory. DATA SOURCES: Literature search was conducted in PubMed for relevant articles published before January 2021. The search aimed to identify recent developments in immune-based treatment approaches for HCC. Information of clinical trials was obtained from https://clinicaltrials.gov/. RESULTS: Two immune checkpoint inhibitors (ICIs), nivolumab and pembrolizumab were approved as monotherapies, which has revolutionized HCC treatment. Besides, combination ICIs have also got accelerated FDA approval recently. Immune-based therapies have challenged targeted drugs owing to their safety, tolerability, and survival benefits. In addition to the significant success in ICIs, other immunotherapeutic strategies such as cancer vaccine, chimeric antigen receptor T-cells, natural killer cells, cytokines, and combination therapy, have also shown promising outcomes in clinical trials. Various diagnostic and prognostic biomarkers have been identified which can help in clinical decision making when starting treatment with ICIs. CONCLUSIONS: Immunotherapy has emerged as one of the mainstream treatment modalities for advanced HCC in recent years. However, challenges such as low response rate and acquired resistance in previously respondent patients still exist. Further research is needed to understand the unique resistance mechanism to immunotherapy and to discover more predictive biomarkers to guide clinical decision making.