Polymorphisms in DNA repair genes may be associated with differences in DNA repair capacity, thereby influencing the individual susceptibility to smoking-related cancer. We investigated the association of 10 nucleotide-excision repair gene polymorphisms ( APE1 Asp148Glu; ) with head and neck cancer risk in North Indian poulations. Genotypes were determined by PCR-RFLP and PCR-single base extension assays in 135 head and Neck cancer patients and 150 age- and sex-matched controls, and the results were analyzed using logistic regression adjusted for relevant covariates. A significant association between the APE1 Asp148Glu polymorphism and head and neck cancer risk was found, with adjusted odds ratios (OR) of 3.38 (p=0.001) for the Asp/Glu genotype and 2.39 (p=0.038) for the Glu/Glu genotype.