The study was conducted to investigate the relationship between vitamin D receptor (VDR) gene rs2228570 and rs1544410 polymorphisms and pancreatic cancer (PC). Two hundred fifty-eight PC patients and 385 healthy controls were enrolled in this study. The genotypes of rs2228570 and rs1544410 were assayed using the polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) method. Univariate and multivariate logistic regression analyses were applied to determine the association between PC-onset risk and VDR gene polymorphisms. Contingency table analysis was performed to evaluate the relationship between the gene polymorphisms and clinicopathological tumor features such as location, pathological differentiation, and the TNM classification of PC. In rs2228570, the T loci and genotypes with T allele could increase the risk of PC; in rs1544410, the G loci and genotypes AG + GG could decrease the onset risk of PC significantly. The contingency table analysis indicated that the rs2228570 polymorphisms were correlated with the pathological differentiation of PC significantly, and the rs1544410 polymorphisms were correlated with the TNM classification of PC significantly. In conclusion, the VDR gene polymorphisms were correlated with incidence, pathological differentiation, and the TNM classification of PC significantly in our study population. So, the VDR polymorphisms have important implications in the incident rate and survival rate of PC.