Background: Polymorphisms altering DNA repair capacity may lead to synergistic effects with tobacco carcinogen-induced lung cancer risk. Based on this hypothesis, the relationship between APEI polymorphism, smoking and the risk of lung cancer was explored. Materials and Methods: The distribution of the APE1 Asp148Glu polymorphisms in 98 lung cancer patients and 67 healthy individuals were compared using PCR-RFLP analysis. Results: Individuals carrying the APE1 Asp148Glu heterozygous and homozygous variant genotype had a 3.23-fold increased risk of lung cancer compared with these carrying the wild-type (Asp/Asp) genotype (P<0.0001), and those carrying the 148Glu homozygous genotype had a 3.17-fold increased risk (p=0.023). When stratified by smoking status, carriers of the Glu allele of APE1 were at a statistically increased risk of lung cancer among smokers (p=0.001). Conclusion: A statistically significant interaction of current smoking status with APE1 Asp148Glu polymorphism was found. These results suggest that the presence of one or two APE1 Glu allele was associated with the risk of developing lung cancer.