To assess the natural variation of hOGG1 gene and the gene-environmental interactions, the hOGG1 codon 326 polymorphism and urinary 8-OHdG levels were investigated in large samples (n = 953) of healthy individuals from five Chinese ethnic populations by using PCR-RFLP and HPLC-ECD. Life-style parameters under study were obtained through a questionnaire. The allelic frequencies of the hOGG1 gene in the Chinese populations were found to be 0.16 (Ser/Ser), 0.49 (Ser/Cys) and 0.35 (Cys/Cys), respectively. The frequencies of Ser326Cys polymorphism were significantly different among the five Chinese ethnic populations (P = 0.002). No association was found between the hOGG1 gene polymorphism and other life-style parameters except for the association between Ser326Cys and smoking (P = 0.027). A significant increase of urinary 8-OHdG level was observed in Cys326Cys allelic healthy subjects (P = 0.033). These results suggest that there are natural variations of hOGG1 gene among Chinese ethnic populations. Smoking relates to Cys/Cys polymorphism frequencies, and oxidative DNA damage is repaired less in individuals with the hOGG1 Cys326Cys genotype.