Taken together, the addition of anti-CTLA-4 with anti-PD-1 immunotherapy produces a statistically significant improvement in OS with a manageable safety profile, providing an alternative option for advanced HCC patients who are not suitable for multi-kinase inhibitors or anti-VEGF, such as in the context of increased bleeding risks commonly found in advanced HCC patients. This evidence concerns the gene CTLA4 and hepatocellular carcinoma.