Abstract: Objective To investigate the correlation of single nucleotide polymorphism of rs3731055 and rs2607775 of xeroderma pigmentosum group C (XPC) and smoking with genetic susceptibility to pancreatic cancer.Methods The clinical data of 214 patients with pancreatic cancer who were admitted to the First and Third Affiliated Hospitals of Xinjiang Medical University from January 2009 to June 2011 and 214 healthly individuals were retrospectively analyzed. The samples of venous blood of 214 patients with pancreatic cancer (case group) and 214 healthy individuals (control group) were analyzed by the Multiplex SNaPshot method. The count data were analyzed using the chisquare test. The association between the single nucleotide polymorphism of rs3731055 and rs2607775 with genetic susceptibility to pancreatic cancer was analyzed using the Logistic regression method. Results Four hundred and twentythree samples of gene were successfully typed, including 210 in the case group and 213 in the control group. The frequency of G allele of XPC rs3731055 was 75.95%(319/420) in the case group and 77.00%(328/426) in the control group, with no significant difference between the 2 groups (χ2=0.12, P>0.05). The frequencies of genotypes GG, GA and AA were 58.57%(123/210), 34.76%(73/210) and 6.67%(14/210) in the case group, and 60.09%(128/213), 33.80%(72/213) and 6.10%(13/213) in the control group, with no significant difference between the 2 groups (χ2=0.12, P>0.05). The frequency of C allele of XPC rs2607775 was 87.86%(369/420) in the case group and 93.43%(398/426) in the control group, with significant difference between the 2 groups (χ2=7.75, P<0.05). The frequencies of genotypes CC, CG and GG were 77.62%(163/210), 20.48%(43/210) and 1.90%(4/210) in the case group, and 86.85%(185/213), 13.15%(28/213) and 0(0/213) in the control group, with significant difference between the 2 groups (χ2=8.54, P<0.05). Patients with rs2607775 GC genotype were associated with a significantly increased risk of pancreatic cancer compared with patients with rs2607775 CC genotype (adjusted OR=1.81, 95% CI: 1.063.10, P<0.05). Patients with rs2607775 GC+GG genotype were associated with a significantly increased risk of pancreatic cancer compared with patients with rs2607775 CC (adjusted OR=1.98, 95% CI: 1.163.36, P<0.05). The ratio of patients in the case group who smoked cigarettes≥17 pack years was 25.24%(53/210), which was significantly higher than 13.15%(28/213) of the control group (χ2=11.37, P<0.05). The results of univariate analysis showed that patients who smoked cigarettes≥17 pack years had higher risk of getting pancreatic cancer (adjusted OR=2.82, 95%CI: 1.276.29, P<0.05). Patients who smoked cigarettes≥17 pack years and with rs2607775 CC also had higher risk of getting pancreatic cancer (adjusted OR=2.87, 95%CI: 1.186.99, P<0.05). No significant geneenvironment interaction was observed between rs2607775 GC+GG and smoking≥17 pack years (adjusted OR=3.65, 95%CI: 0.6720.03, P>0.05). Conclusions The polymorphisms of XPC rs2607775 may play a role in the onset of pancreatic cancer. Patients who smoke cigarettes≥17 pack years are more easily to have pancreatic cancer. There is no interaction between smoking and XPC rs2607775 in influencing the progression of pancreatic cancer.