The objective of the present study was to determine the codon 72 genotypic frequencies of p53 in Indian women and to analyze the association of this polymorphism with human papillomavirus (HPV) related cervical cancer (CaCx). We used tissues derived from 55 women diagnosed with squamous cell carcinoma of the cervix (of whom 46 were HPV types 16/18 positive) and cervical scrapes derived from 201 cytologically normal women (of whom 84 were HPV types 16/18 positive) as controls. The DNA isolated from these samples was genotyped for p53 polymorphism by polymerase chain reaction and restriction fragment length polymorphism method. The genotypic frequency of homozygous arginine among women with CaCx was 27% and this did not differ with the controls. But, proline homozygosity of 33% in the malignant samples was significantly higher than controls (OR=2.23; 95% CI: 1.14-4.35; P=0.02). The associated risk of this genotype towards CaCx was more prominent (OR=2.67; 95% CI: 1.16-6.15; P=0.02) when analysis was restricted to HPV 16/18 positive women. Thus, proline homozygosity at codon 72 of p53 and not arginine homozygosity, could be a risk factor for development of CaCx associated with high risk HPV among Indian women.