Since the initial testing of the first inhibitor of the immune checkpoint, cytotoxic T lymphocyte-associated protein 4 (CTLA-4), against HCC in 2008 (9), subsequent discoveries have unveiled a series of immune checkpoints, including programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1), lymphocyte activation gene 3 (LAG-3), and T cell immunoglobulin and mucin-domain containing-3 (Tim-3). This evidence concerns the gene CD274 and hepatocellular carcinoma.