Polymorphisms in DNA repair genes may be associated with differences in the repair capacity of DNA damage and may thereby influence an individual's susceptibility to smoking-related cancer. We investigated the association between the -93G-->A polymorphism in the hMLH1 gene and the risk of lung cancer in a Korean population. The hMLH1 -93G-->A polymorphism was typed in 372 lung cancer patients and 371 healthy controls that were frequency-matched for age and sex. There was no significant association between the hMLH1 -93G-->A genotype and the risk for adenocarcinoma or small cell carcinoma. However, the AA genotype was associated with a significantly increased risk for squamous cell carcinoma compared with both the GG genotype (adjusted OR=2.02; 95% CI=1.15-3.55; p=0.014) and the combined GG and GA genotype (adjusted OR=1.83; 95% CI=1.24-2.71; p=0.003). When the subjects were stratified by smoking exposure, the AA genotype was associated with a significantly increased risk for squamous cell carcinoma in lighter smokers (< or = 39 pack-years; adjusted OR=1.95; 95% CI=1.03-3.66; p=0.039) compared with the combined GG and GA genotype, whereas there was no significant association in heavier smokers (> 39 pack-years; adjusted OR=1.47; 95% CI=0.82-2.61). These results suggest that the hMLH1 -93G-->A polymorphism could be used as a marker of genetic susceptibility to squamous cell carcinoma of the lung.