A common polymorphism at codon 72 of TP53, the gene encoding the tumor suppressor protein p53, encodes either arginine or proline. These variants may be associated with tumor susceptibility since they interfere with the ability of TP53 to activate apoptosis, and might account for ethnic variation in cancer frequency. Using a polymerase chain reaction-restriction fragment length polymorphism assay, we tested peripheral blood samples from 115 patients with nasopharyngeal carcinoma (NPC) and from 83 healthy individuals. Patients with NPC (Arg/Arg = 38.26%, Arg/Pro = 41.73%, and Pro/Pro = 20%) showed a significantly different percentage of the Pro/Pro genotype, compared with the control population (Arg/Arg = 39%, Arg/Pro = 54%, and Pro/Pro = 7%) (P = 0.0307). No significant difference was observed between TP53 codon 72 polymorphism and age, sex, histological grade, and metastasis. These results provide evidence that individuals with the Pro/Pro genotype have an increased risk of developing NPC in Tunisia.