Objective To explore the molecular mechanism by which SOS Ras/Rac guanine nucleotide exchange factor 1-intronic transcript 1 (SOS1-IT1) affects enhancer of zeste homolog 2 (EZH2) protein expression in endometrial cancer cells Ishikawa and RL95-2.   Methods  Lentiviral transfection of short hairpin RNA(shRNA) and overexpression plasmid were used in Ishikawa and RL95-2 cell lines to knock down and overexpress SOS1-IT1. The mechanism of EZH2 expression regulation was studied using Real-time PCR, Western blotting, and chromatin immunoprecipitation.  Results The expression of SOS1-IT1 and EZH2 genes was positively correlated in endometrial cancer tissues. Knocking down SOS1-IT1 significantly reduces the expression of EZH2, inhibited the proliferation and migration of Ishikawa and RL95-2 cells, and could reduced the acetylation of histone H3 at position 27 (H3K27) and the enrichment of CREB binding protein (CBP) in the EZH2 gene promoter region. Overexpression of SOS1-IT1 could increased the expression of EZH2 and enhance the acetylation of H3K27 and the enrichment of CBP. CBP could bind to SOS1-IT1 RNA, and this binding ability was weakened when CBP was knocked down. Conclusion   SOS1-IT1 can promote the expression level of EZH2 in endometrial cancer cells Ishikawa and RL95-2 by regulating the acetylation modification level of the EZH2 gene promoter region, thereby affecting the proliferation and migration ability of endometrial cancer cells.