In this study, we used GSK5959, a BRPF1-specific inhibitor, and pan-BRPF inhibitors OF-1 and NI-57 for supplementary evidence to demonstrate that pharmacological inactivation of BRPF1 induced cell cycle arrest and cellular senescence, inhibited liver cancer stemness in vitro and significantly suppressed HCC tumor growth in vivo. This evidence concerns the gene BRPF1 and hepatocellular carcinoma.