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The DNA damage, caused by cigarette smoking, can cause airway cell apoptosis and death,which may be associated with the development of chronic obstructive pulmonary disease (COPD).However, just 20%-30% smokers develop COPD, which suggests that different degrees of DNA repair cause different outcomes in smokers. X-ray repair cross-complementing group 1 (XRCC1), a base exci-sion repair protein, has multiple roles in repairing ROS-mediated, basal DNA damage and single-strand DNA breaks. The present study investigated the association between polymorphism in XRCC1 (Arg399Gln) and susceptibility of COPD. A total of 201 COPD cases and 309 controls were recruited and frequency-matched on age and sex. XRCC1 genotype was determined by PCR-restrietion fragment length polymorphism analysis. Overall, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD had no significant difference among individuals with Trp/Trp genotype. However, after stratifying by smoking status, in former smokers, compared with those with the XRCC1 Arg/Arg geno-type, the risk for COPD was significantly reduced among individuals with Trp/Trp genotype (adjusted OR=0.22, 95% CI 0.06-0.85, P=0.028); after stratifying by smoking exposure, in light smokers, com-pared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Arg/Trp genotype and Trp/Trp genotype (adjusted OR=0.39, 95% CI 0.16-0.94,P=0.036; 0.24, 95% CI 0.07-0.79, P=0.019, respectively). In conclusion, XRCC1 Arg194Trp genotype is associated with a reduced risk of developing COPD among former and light smokers.