DNA repair plays a critical role in protecting the genome of the cell from the insults of cancer-causing agentssuch 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 polymorphismsmay affect DNA repair capacity and thus modulate cancer susceptibility in exposed populations. In the presentstudy, we explored the relationship between polymorphisms in the DNA repair gene XRCC1399 and hOGG1326genotypes using polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) and risk ofcancer development. 156 smokeless tobacco users and 70 controls without significant exposure to mutagenswere 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 ofgenetic damage. There were significant differences in the micronucleus (MN), Comet scores and chromosomalaberrations (CA) between smokeless tobacco users and control subjects by Student’s t-test (P<0.05). Thesefindings provide evidence for the view that polymorphisms in DNA repair genes may modify individualsusceptibility to tobacco related cancers and justify additional studies to investigate their potential role indevelopment of cancer.