Abstract: The overexpression of of Zeste enhancer homolog 2 (EZH2) is closely associated with tumor initiation, progression, invasion, metastasis, and unfavorable clinical prognosis. EZH2 plays a crucial role in the transcriptional repression of tumor-related genes and the regulation of tumorigenesis and development through various mechanisms, including PRC2-dependent H3K27 methylation or non-histone methylation, PRC2-independent non-histone methylation, direct protein-protein interactions, etc, to activate downstream genes. Therefore, EZH2 is considered to be a promising therapeutic target for tumor treatment. Currently, the development and clinical trials of small molecule inhibitors targeting EZH2 have emerged as a prominent area of research. This article reviews functions and regulatory mechanisms of EZH2 and highlights recent advancements in hotspot inhibitors, aiming to provide valuable insights for further research and application in diverse cancer treatments.