Polymorphisms in DNA repair genes may be associated with differences in repair capacity of DNA damage and may thereby influence an individual's susceptibility to lung cancer. We investigated the association between the -93G-->A polymorphism in the mismatch repair hMLH1 gene for its role in the susceptibility and survival of non-small cell lung cancer (NSCLC) patients. Using a case-control study design, 165 NSCLC patients and 193 controls with similar range for age, gender and smoking habit distributions were subjected to genotype analysis. The risk of lung cancer was estimated by logistic regression analysis. The Kaplan-Meier method was used to estimate the probability of survival and the log-rank test was used to assess the significance of the difference between survival probabilities. The homozygous variant A/A genotype was associated with a significantly increased risk for lung cancer compared with the other genotypes (Crude analysis P=0.003, Adjusted analysis P=0.011, using the logistic regression model). The patients with a homozygous variant A/A genotype had a trend toward poorer prognoses compared with other patients, especially smoking (P=0.05, by log-rank test), male (P=0.06), or squamous carcinoma (P=0.08) patients. This is the first case-control study to show a significant association between the hMLH1-93G-->A polymorphism and the susceptibility to and prognosis of lung cancer. The results herein may be useful for risk assessment and disease monitoring of NSCLC.