Objective: To investigate the effects and mechanisms of zinc finger E-box binding homeobox transcription factor-2 ( ZEB 2) on the proliferation, colony formation, migration, and invasion abilities and the epithelial-mesenchymal transition (EMT) of PANC-1 cells, a human pancreatic cancer cell line., Methods: Data on the expression of ZEB 2 in pancreatic cancer tissues and paracancerous tissues from The Cancer Genome Atlas (TCGA) database were analyzed. PANC-1 pancreatic cancer cells were divided into si-NC group, si- ZEB 2 group, pcDNA3.1 group, and pcDNA3.1- ZEB 2 group. qRT-PCR and Western blot were conducted to confirm the effectiveness of ZEB 2 knockdown or overexpression. CCK-8, colony formation, wound healing, and Transwell assays were conducted to examine the effects of ZEB 2 on the proliferation, colony formation, migration, and invasion of PANC-1 cells. qRT-PCR and immunofluorescence assays were performed to examine the expression of E-cadherin and vimentin, the EMT markers, in the cells. Prediction of proteins interacting with ZEB2 was made through the STRING database., Results: TCGA database analysis showed that the expression level of ZEB 2 in pancreatic cancer tissues was significantly higher than that in adjacent tissues ( P <0.05). Compared with those of cells in the control group, the proliferation, colony formation, migration, and invasion of cells in the si- ZEB 2 group were decreased ( P <0.05). Compared with those of cells in the pcDNA3.1 group, the proliferation, colony formation, migration and invasion of cells in the pcDNA3.1- ZEB 2 group were increased (all P <0.05). According to the results of qRT-PCR and immunofluorescence assays, compared with those of the si-NC group, the expression of E-cadherin mRNA, an epithelial marker, in the si- ZEB 2 group increased, while the expression of vimentin mRNA, an mesenchymal marker, and the protein decreased. Compared with those of the pcDNA3.1 group, the expression of E-cadherin mRNA in the PANC-1 cells of the pcDNA3.1- ZEB 2 group decreased, while the expression of vimentin mRNA and the protein increased (all P <0.05). Analysis with the STRING database predicted that 10 proteins had close interaction with ZEB2., Conclusion: Overexpression of ZEB 2 promotes the migration, invasion, and the EMT process of PANC-1 pancreatic cancer cells., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)