Cheng et al. suggest that BRPF1 plays an oncogenic role in hepatocellular carcinoma (HCC), by controlling histone acetylation in the promoter regions of E2F2 and EZH2. Its high levels are correlated with poor survival in HCC patients, and targeting it might serve as a strategy for cancer treatment. Here, EZH2 is linked to hepatocellular carcinoma.