T cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) is a novel transmembrane protein that is involved in the regulation of T-helper 1 cell-mediated immunity. Studies have shown that polymorphisms in TIM-3 gene can be associated with various diseases. Here, we investigated the correlation of TIM-3 polymorphisms with susceptibility to pancreatic cancer in the Chinese population. Three polymorphisms in TIM-3 gene (-1516G/T, -574G/T, and +4259T/G) were identified by polymerase chain reaction-restriction fragment length polymorphism in 306 pancreatic patients and 408 healthy controls. Results showed that the prevalence of +4259TG genotype and +4259G allele were significantly increased in the pancreatic cancer cases than in controls [odds ratio (OR) = 2.82, 95 % confidence interval (CI), 1.45-5.48, p = 0.0015, and OR = 2.74, 95 % CI, 1.42-2.94, p = 0.0017]. In addition, when analyzing the TIM-3 polymorphisms with different clinical parameters in pancreatic cancer patients, the cases with vascular infiltration had higher numbers of +4259T/G polymorphism than those without vascular infiltration (OR = 3.07, 95 % CI, 1.41-6.68, p = 0.003). These results suggested polymorphisms in TIM-3 gene could be new risk factors for the development of pancreatic cancer.