Abstract: EZH2 (enhancer of zeste homolog 2) can change the expression of downstream target genes by methylating lysine at position 27 of histone 3 (H3K27me3), and participate in DNA methylation to inhibit gene transcription so as to inhibit the growth of tumor cells. In recent years, the role of EZH2 in cancer pathophysiology has received extensive attention and in-depth research. The launch of tzemetostat, the first EZH2 inhibitor in the world, is a milestone. In this article, the structure and mode of action of EZH2 are summarized, and the global preclinical/clinical research progress of EZH2 inhibitors is highlighted, aiming to provide reference for the development of new EZH2 inhibitors.