Liver cancer is the third most common cause of cancer-associated death. Advances in the last decade have provided more options for treating hepatocellular carcinoma. The use of immune checkpoint inhibitors represents a leap forward and broadens the armamentarium for clinicians. In this article, we provide a state-of-the-art review of molecular therapy. We also detail the mechanisms of checkpoint inhibitor therapy, which blocks the interaction of programmed cell death receptor protein with programmed cell death ligand, reducing the immune checkpoint activity on regulatory T cells, thereby inhibiting tumor cell growth.