Histone modification, an important epigenetic mechanism, is related to the carcinogenesis of hepatocellular carcinoma (HCC). In three datasets, we screened 88 epigenetic-dysregulated PCGs (epi-PCGs) , which were significantly associated with HCC survival and could cluster HCC into three molecular subtypes. These subtypes were associated with prognosis, immunomodulatory alterations, and response to different treatment strategies. Based on 88 epi-PCGs in the TCGA training set, a risk prediction model composed of 4 epi-PCGs was established. The model was closely related to the clinicopathological features and showed a strong predictive ability in different clinical subgroups. In addition, the risk prediction model was an independent prognostic factor for patients with HCC. The significance of epi-PCGs in HCC is revealed by our data analysis.