DNA repair plays a critical role in protecting the genome of the cell from the insults of cancer-causing agents such as those found in tobacco. Reduced DNA repair capacity may constitute a significant risk factor for cancers. Recently, a number of polymorphisms in several DNA repair genes have been discovered, these polymorphisms may affect DNA repair capacity and thus modulate cancer susceptibility in exposed populations. In the present study, we explored the relationship between polymorphisms in the DNA repair gene XRCC1399 and hOGG1326 genotypes using polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) and risk of cancer development. 156 smokeless tobacco users and 70 controls without significant exposure to mutagens were recruited. Questionnaires were completed to obtain detailed occupational, smoking, and medical histories. A standard micronucleus assay, comet assay and chromosomal aberration assays were used as a marker of genetic damage. There were significant differences in the micronucleus (MN), Comet scores and chromosomal aberrations (CA) between smokeless tobacco users and control subjects by Student's t-test (P< 0.05). These findings provide evidence for the view that polymorphisms in DNA repair genes may modify individual susceptibility to tobacco related cancers and justify additional studies to investigate their potential role in development of cancer.