DNA repair enzymes play an important role in the development of various kinds of cancer. We hereanalyzed associations of XPD Lys751Gln, APEX1 Asp148Glu, XRCC1 Arg399Gln, and XRCC3 Thr241Metgene polymorphisms in DNA repair pathways in relation to the risk of lung cancer using PCR-RFLP. The studyinvolved 104 lung cancer patients and 120 non-cancer controls divided into non-smokers and smokers. Wefound a statistically significant interaction between APEX1 Asp148Glu and the risk for lung cancer (adjustedOR 2.78, 95% CI 1.58-4.90, p=0.0004), of both adenocarcinoma (adjusted OR 2.24, 95%CI 1.18-4.25, p=0.014)and squamous cell carcinoma (adjusted OR 4.75, 95%CI 1.79-12.60, p=0.002) types. XRCC1 Arg399Gln showeda borderline significant association with adenocarcinoma (adjusted OR 1.89, 95%CI 1.00-3.57, p=0.051). Thecombined effect of smoking and presence of the APEX1 Asp148Glu demonstrated a significant association withrisk of lung cancer (adjusted OR 3.61, 95% CI 1.74-7.50, p = 0.001). The XPD Lys751Gln and XRCC3 Thr241Metgenotypes displayed no statistically significant risk. Our findings suggest that the APEX1 Asp148Glu is associatedwith increased risk for primary lung cancer in Japanese individuals partaking in smoking.