Overall, our study investigated the roles of EZH2 in the immune functions of DCs and the epigenetic mechanisms of EZH2 in FHF, suggesting that EZH2 promotes the development of liver failure in FHF, which was verified with Ezh2D−/− mice and ameliorated using the inhibitor GSK126, via modulation of immune responses. This evidence concerns the gene EZH2 and liver failure.