Pancreatic cancer (PC) is one of the most common malignant tumors in digestive tract. To explore the role of epigenetic factorEZH2in the malignant proliferation of PC, so as to provide effective medical help in PC. Sixty paraffin sections of PC were collected and the expression ofEZH2in PC tissues was detected by immunohistochemical assay. Three normal pancreas tissue samples were used as controls. The regulation ofEZH2gene on proliferation and migration of normal pancreatic cell and PC cell were determined by MTS, colony forming, Ki-67 antibody, scratch and Transwell assays. Through differential gene annotation and differential gene signaling pathway analysis, differentially expressed genes related to cell proliferation were selected and verified by RT-qPCR.EZH2is mainly expressed in the nuclei of pancreatic tumor cells, but not in normal pancreatic cells. The results of cell function experiments showed thatEZH2overexpression could enhance the proliferation and migration ability of PC cell BXPC-3. Cell proliferation ability increased by 38% compared to the control group.EZH2knockdown resulted in reduced proliferation and migration ability of cells. Compared with control, proliferation ability of cells reduced by 16%-40%. The results of bioinformatics analysis of transcriptome data and RT-qPCR demonstrated thatEZH2could regulate the expression ofE2F1,GLI1,CDK3andMcm4in normal and PC cells. The results revealed thatEZH2might regulate the proliferation of normal pancreatic cell and PC cell throughE2F1,GLI1,CDK3andMcm4.Supplementary InformationThe online version contains supplementary material available at 10.1186/s41065-023-00280-1.