To identify the risk factors other than tobacco and alcohol for the development of head and neck cancer, functional polymorphisms of DNA repair genes including XRCC1 Arg194Trp in the exon 6, Arg280His in the exon 9, Arg399Gln in the exon 10, XRCC2 Arg188His in the exon 3, XRCC3 Thr241Met in the exon 7, XRCC4 codon 247, XRCC4 G1394T, XRCC4 intron7, XRCC5 2R/1R/0R, XRCC6 61 (C>G) and XRCC7 6721 (G>T) were studied among rural population of Maharashtra. The XRCC genes were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to elucidate the specific changes in the gene region. The result from our study showed that XRCC1 A399G in exon 10 (OR= 3.69; 95%CI= (2.34-5.51); p= <0.0001) XRCC4-2 (G1394T) OR=6.53; 95%CI=(4.71-9.05); p= <0.0001), XRCC5 (0R/0R) OR=1.97; 95%CI=(1.15-3.26); p= <0.0001) and XRCC7 (6721 T/T) OR=11.58; 95%CI=(7.44-18.02); p= <0.0001) genotypes significantly increased the risk of head and neck cancer. This study indicates that variant types of XRCC1, XRCC4, XRCCC5 and XRCC7 genes play a role in modifying genetic susceptibility of individual to head and neck cancer. Thus, the consistent findings from this case-control study suggest that selected DNA repair genes represent genetic determinants in oral carcinogenesis along with other risk factors in the rural Indian population.