XRCC2 is an essential part of the homologous recombination repair pathway. However, relatively little is known about the effect of XRCC2 gene C41657T and G4234C polymorphisms on the individual susceptibility to colorectal cancer (CRC). The purpose of this study was to investigate the association between XRCC2 gene C41657T and G4234C polymorphisms and CRC and to explore the relationship among the polymorphisms and clinicopathologic parameters and protein expression levels of XRCC2. A hospital-based case-control study was conducted with 246 CRC cases and 262 healthy controls. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. XRCC2 protein was analyzed by immunohistochemistry for the paraffin sections of 120 CRC cases. The study data showed that the C41657T genotypes were associated with the risk of CRC. The CT/TT genotypes and T allele were overrepresented among the CRC cases. Compared with CC, CT/TT enhanced the risk of CRC (odds ratio = 1.646, 95 % confidence interval = 1.127-2.404, P = 0.010). XRCC2 protein expression of CRC patients with CT/TT genotypes was significantly higher than that of the patients with CC genotype (χ (2) = 4.887, P = 0.027). XRCC2 gene G4234C polymorphisms have no relevance to the risk of CRC. Our findings suggest that XRCC2 C41657T polymorphism may adjust the XRCC2 expression and might influence susceptibility of CRC.