In the present case control study mRNA expression of the GSTP1 gene, encoding a phase II enzyme thatdetoxifies via glutathione conjugation, was investigated using semiquantitative PCR followed by SSCP for 49confirmed head and neck (HN) cancer and 49 control samples. It was found that GSTP1 was upregulated insignificantly higher number of cancers (OR 4.2, 95% CI 1.2- 15.3). Grade wise correlation was also observedwith more up regulation in patients with more advanced grades of HN carcinomas. We also found that 5 patientsshowed variation in mRNA with a larger product size than expected. Sequencing revealed insertion of an intronicsegment between the 6th and 7th exon of the GSTP1 gene. Germline screening was performed showing mobilityshifts which suggested mutation at the DNA level resulting in intronic portion retention. This study is of primeimportance for drug design and treatment selection to overcome increased resistance of HN cancers to drugsdue to alteration in the GSTP1 gene.