Currently, the main combination strategies in HCC include: (1) ICIs combined with other immune checkpoint blockade, such as PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitors, to enhance T cell activation and overcome tumor immune escape; (2) ICIs combined with locoregional therapies, which can promote antigen release and strengthen immune responses; (3) ICIs combined with targeted therapies, such as anti-angiogenic agents or TKIs, which help normalize tumor vasculature, increase T cell infiltration, improve the immune microenvironment, and overcome resistance. This evidence concerns the gene CTLA4 and hepatocellular carcinoma.