During the past three years, the management of hepatocellular carcinoma (HCC) has been drastically improved with the application of immunotherapy, especially after the advent of immune checkpoint inhibitors (ICIs), namely antibodies targeting the programmed cell death receptor-1 (PD-1), the anti-programmed death 1 ligand (PD-L1), the cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4), and most recently, the LAG-3 (Lymphocyte-activation-gene-3). This evidence concerns the gene CTLA4 and hepatocellular carcinoma.