In an effort to understand the mechanism of action, we found that inhibition of EZH2 by chidamide or shEZH2 decreased the levels of H3K27me3 and DNMT3A and increased the cytotoxic activity of adriamycin, and EZH2 overexpression had the opposite effects on AML cells. Here, EZH2 is linked to acute myeloid leukemia.