This study was carried out to investigate the association of cytochrome P450 2C9 (CYP2C9) gene polymorphism with squamous cell carcinoma (SCC) of oropharynx & hypopharynx. One hundred ten males suffering from locally advanced squamous cell carcinoma and an equal number of healthy controls were genotyped for CYP2C9*2 and CYP2C9*3, leading to poor metabolizers (PMs) by PCR–based RFLP. The frequency of genotypes of CYP2C9*2 (40%) and CYP2C9*3 (16%) were found to be significantly higher in the HNSCC controls as compared to the cases. The data suggests a significant association of the CYP2C9 polymorphism with SCC of oro & hypopharynx and underlining the importance of genotyping in determining the risk of occurrence of SCC of oropharynx & hypopharynx