Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and catalytic component of PRC2, catalyzes the tri-methylation of histone H3 at LYS27 ( H3K27me3 ) to regulate gene expression through epigenetic machinery, and is a member of the polycomb group of proteins. EZH2 is involved in the epigenetic inhibition of the expressions of numerous tumor suppressor genes, regulation of the cell cycle, promotion of cell proliferation, and cell invasion. The tumor microenvironment is related to the occurrence of tumors, tumor development, and prognosis. Recently, many studies have reported that EZH2 is expressed in a variety of immune cells and regulates the tumor microenvironment. It is also an essential component of immune responses and anti-tumor immunity. We summarize the function of EZH2 in different cell types and explore its potential as a tumor immunotherapy target.