Lung cancer is one of the most spread cancers in the world. The X-ray repair cross-complementing group 1 (XRCC1) gene plays an important role in the development of lung cancer. The objective of this study is to investigate the potential association of XRCC1 genetic polymorphisms with the susceptibility to lung cancer. In totally, 361 lung cancer patients (male, 276; female, 85; mean age, 62.55) and 361 cancer-free controls (male, 253; female, 108; mean age, 61.33) were enrolled in this case-control study. The genotypes of XRCC1 c.1471G>A genetic polymorphism were determined by the created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. The influence of XRCC1 gene on the susceptibility to lung cancer was analyzed by the analyses association. Our data indicated that significant differences were found in the frequencies of allelic and genotypic between lung cancer patients and cancer-free controls. The c.1471G>A genetic polymorphism was statistically associated with increased susceptibility to lung cancer [AA vs. GG: odds ratio (OR)=2.75, 95 % confidence interval (CI) = 1.55-4.88, P<0.001; AA vs.
Ga/gg: OR=2.69, 95 % CI=1.55-4.69, P<0.001; A vs. G: OR=1.37, 95 % CI=1.09-1.71, P=0.007]. The allele A and genotype AA may contribute to the susceptibility to lung cancer. Taken together, these results showed that the functional c.1471G>A genetic polymorphism of XRCC1 was associated with lung cancer susceptibility in the studied population.