Objectives: Squamous cell carcinoma is the most common cancer of the oral cavity, and several etiologic factors are involved in its development. Single nucleotide polymorphism (SNP) of the P 53 gene codon 72 ( P 53c72) changes the structure of the protein and affects its activity. The prevalence of P 53c72 different genotypes, which seems to vary with race and geographic location, has shown a strong correlation with many types of human cancers. The aim of this study was to investigate the correlation between P 53c72 polymorphism and risk of oral squamous cell carcinoma (OSCC) in the heavily populated Gilan Province in northern Iran. Design of S tudy: This case-control study was done on 55 paraffin-embedded samples from OSCC patients and 100 samples of non-dysplastic oral cavity lesions. The P 53c72 genotypes were determined using the ARMS-PCR method. SPSS-15 software was used for statistical analysis. Results: There were no significant statistical differences found between the prevalence of different P 53c72 genotypes in the OSCC group vs. the control. However, the Pro/Pro genotype in OSCC samples showed a strong correlation with age, as 70% of such patients were below 50 years old. Interestingly, a large portion (40%) of the patients with the Pro/Pro genotype had the tumor in the lip area. Conclusions: Although P 53c72 polymorphism does not appear to be a predisposing factor for OSCC in the population of Northern Iran, the Pro/Pro genotype could be considered as a risk factor for OSCC in adults below 50 years old and the anatomical location of the tumor.