Therefore, we propose a novel mechanism of oncogene inactivation in HCC that regulates histone and DNA methylation at the epigenetic level to affect transcription, where the selective splice variants of EZH2 antagonize the function of its full-length isoform and repress H3K27me3 methylation, thereby altering the expression of the oncogene. The gene discussed is EZH2; the disease is hepatocellular carcinoma.