BACKGROUND Oral squamous cell carcinoma (OSCC) is a multifactorial neoplasm related to tobacco smoke, alcohol consumption and molecular genetic changes such as p53 mutations. The human tumor suppressor gene TP53 contains single nucleotide polymorphism that encodes either arginin (Arg) or proline (Pro) at amino acid codon 72 of the p53 protein. The relationship between human cancer susceptibility and p53 polymorphism at codon 72 is controversial. The aim of this study was to investigate the association between this polymorphism and OSCC development in a Brazilian population. METHODS Eighty-two patients with OSCC and 82 age-sex-matched controls were included in the study. DNA was extracted from all subjects' normal oral mucosa and the polymerase chain reaction amplification (PCR) was performed for detection of the TP53 genotypes. PCR products were analyzed in a 6.5% polycrylamide gel and silver-stained. Statistical analyses were performed with the chi 2 test and Fisher's exact test. RESULTS The frequencies of the genotypes Arg/Arg, Arg/Pro and Pro/Pro, were 37.8%, 54.8% and 7.4%, respectively, for OSCC cases and 40.2%, 54.8% and 4.9% for controls. No significant differences in the distribution of TP53 genotypes were seen between the groups (p = 0.794). CONCLUSIONS The present study does not support the hypothesis that this TP53 polymorphism is associated with oral cancer susceptibility.