ABSTRACT. We performed a study to evaluate X-ray repair crosscomplementing protein 4 (XRCC4) gene polymorphisms and the development of pancreatic cancer. A case-control study including 206 patients with newly diagnosed primary pancreatic cancer and 412 controls was performed between January 2011 and October 2013 in a Chinese population. Genotypes of XRCC4 rs1805377, rs2075685, rs2075686 and rs1056503 were determined using polymerase chain reaction combined with a restriction fragment length polymorphism assay. Compared with controls, pancreatic cancer patients were more likely to have a higher body mass index, family history of cancer, and a habit of alcohol drinking compared with controls (P < 0.05). Logistic regression analysis showed that individuals carrying the TT genotype of XRCC4 rs2075685 had an increased risk of pancreatic cancer compared to those with the GG genotype, with an odds ratio (95% confidence interval) of 1.88 (1.15-3.08 XRCC4 rs2075685 polymorphism could influence the susceptibility to pancreatic cancer in a Chinese population.