Despite improvements in surgical procedures and comprehensive therapies, pancreatic cancer remains one of the most aggressive and deadly human malignancies. It is therefore necessary to determine which cellular mediators associate with prognosis in pancreatic cancer so as to improve the treatment of this disease. In the present study, mRNA array and immunohistochemical analyses showed that KLF5 is highly expressed in tissue samples from three short-surviving patients with pancreatic cancer. Survival analysis using data from The Cancer Genome Atlas showed that patients highly expressing KLF5 exhibited shorter overall and tumor-free survival times. Mechanistically, KLF5 promoted expression of E2F1, cyclin D1 and Rad51, while inhibiting expression of p16 in pancreatic cancer cells. Finally, flow cytometric analyses verified that KLF5 promotes G1/S progression of the cell cycle in pancreatic cancer cells. Collectively, these findings demonstrate that KLF5 is an important prognostic biomarker in pancreatic cancer patients, and they shed light on the molecular mechanism by which KLF5 stimulates cell cycle progression in pancreatic cancer.