Hepatocellular Carcinoma (HCC) is one of the most common malignancies, and its incidence and mortality are increasing worldwide. Cancer immunotherapy has revolutionized cancer treatment in recent years. In particular, immune checkpoint inhibitors (ICIs), as new therapeutic tools, have demonstrated encouraging antitumor activity and manageable tolerability in HCC. Immune checkpoint blockade with antibodies targeting Programmed cell Death-1 (PD-1), Programmed cell Death Ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated protein-4 (CTLA- 4) enhances tumor immunity by restoring exhausted T cells. Although the efficacy of combinational treatment strategies using ICIs combined with other ICIs, molecularly targeted agents, systemic therapy, or locoregional therapy has been well documented in numerous preclinical and clinical studies in several types of cancer, most HCC patients do not benefit from ICI treatment. This review highlights recent developments and potential opportunities related to ICIs and their combination in the management of HCC. The present article also reviews recent patents related to ICIs.