The N-myc downstream regulated gene 1 (NDRG1) is differently expressed in human malignancies according to the tumor type. We investigated the expression of NDRG1 in pancreatic cancer tissues and cell lines as well as how it affects tumor growth, invasion and migration in pancreatic cancer cells. Experimental groups included NDRG1 overexpression and knockdown pancreatic cancer cell lines. Lentivirus-based empty vector transfected cells (NC group) were considered control groups. Proliferation, invasion and migration related proteins such as STAT3, MMPs, PTEN, PI3K/AKT were assessed by CCK-8, Transwell assay and western blotting. Efficient NDRG1 overexpression results in reduced cell proliferation, invasion and migration. Inversely, downregulation of NDRG1 promoted proliferation, invasion and migration. We also found NDRG1 could deactivate p-STAT3, PI3K, p-AKT, MMP2, MMP9 and activate PTEN. NDRG1 is a potential anti-oncogene. Its upregulation significantly decreases pancreatic cancer tumorigenesis, likely by inhibiting STAT3 and the PI3K/AKT signaling pathway.