These data indicated that inhibition of EZH2 either pharmacologically by chidamide or genetically by shEZH2 decreased the activity of Smo/Gli-1 pathway and increased adriamycin sensitivity, and genetic EZH2 overexpression reduced the cytotoxicity of chidamide and restored the resistance to adriamycin in AML cells. Here, EZH2 is linked to acute myeloid leukemia.