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Pancreatic ductal adenocarcinoma is one of the deadliest malignant tumors,and many genes play important roles in its development.The hepatocyte nuclear factor-1a (HNF-1a)gene encodes HNF-1a,which is a transcriptional activator.HNF-1a regulates the tissue-specific expression of multiple genes,especially in pancreatic islet cells and in the liver.However,the role of the HNF-1a gene in the development of pancreatic cancer is still unclear.Here,we used immunohistochemical staining and real-time PCR to analyze HNF-1a expression in pancreatic cancer tissue.Stable cell lines with HNF-1a knockdown or overexpression were established to analyze the role of HNF-1a in pancreatic cancer cell proliferation and apoptosis by colony formation assay and flow cytometry.We also analyzed the L-type pyruvate kinase (PKLR) promoter sequence to identify the regulatory effect of HNF-1a on PKLR transcription and confirmed the HNF-1a binding site in the PKLR promoter via a chromatin immunoprecipitation assay.HNF-1a was found to be overexpressed in pancreatic cancer and promoted proliferation while inhibiting apoptosis in pancreatic cancer cells.PKLR was identified as the downstream target gene of HNF-1a and binding of HNF-1a at two sites in PKLR (-1931/-1926 and-966/-961) regulated PKLR transcription.In conclusion,HNF-1a is overexpressed in pancreatic cancer,and the transcription factor HNF-1a can promote pancreatic cancer growth and apoptosis resistance via its target gene PKLR.