Polymorphisms in DNA repair and apoptosis genes are suspected to alter the individual susceptibility to develop lung cancer. We investigated the relationship between polymorphisms in ATM (A60G), ERCC1 (Asn118Asn), APE1 (Asn148Glu) and iASPP (A67T) and the risk of developing lung cancer. A case-control study was conducted with 315 patients with lung cancer and 315 cancer-free controls, matched on age and sex. Genotypes were detected using the ABI 7500 real-time PCR system. The T/T homozygote in ERCC1 (Asn118Asn) was correlated with a strong statistically significant increased risk of developing lung cancer (adjusted OR=2.44; 95% CI=1.13-5.28; P=0.023), especially lung adenocarcinoma (adjusted OR=3.18) and small cell lung cancer (adjusted OR=6.08). For iASPP (A67T), smokers with at least one T allele (A/T+T/T) were more likely to develop lung cancer (95% CI, 1.07-2.84, P=0.026). Subjects carrying the G allele in APE1 (Asn148Glu) had a decreased risk of lung cancer (P<0.05), which showing a protective effect. Our results suggest that polymorphism Asn118Asn in ERCC1, A67T in iASPP and Asn148Glu in APE1 may associated with early onset of lung cancer as well as some specific subtype of lung cancer. Detection of these biomarkers may be helpful for screening this high-risk population for primary preventing.