Nasopharyngeal carcinoma (NPC) is a serious cancer in Thailand. To address on the genetic risk factor for NPC, we investigated association between the p53 codon 72 polymorphism (Pro/Arg) and NPC susceptibility in the Thai. The genotype frequency of this polymorphism in 102 NPC patients and 148 age-matched healthy controls was determined by using a PCR-RFLP assay. No statistically significant difference in the overall genotype frequencies or allele frequencies between cases and controls was observed. Among NPC patients, no statistical significant difference in p53 genotype frequencies between sex, histological types and clinical stages was observed. When cases and controls were categorized into 3 groups of age, >40, >45 and >50 years, the frequencies of p53 genotype in the cases were significantly different from those of the controls (P<0.05). The p53 Pro homozygotes with age of >40 years had twofold to threefold higher risk to develop NPC and the risk was increased with age (Odds Ratio (OR) increased from 2.01 to 2.63 by age >40 to >50 years). Individuals of age >40, >45 and >50 years with an Arg/Arg genotype and of age >45 and >50 years with combined Arg/Arg or Arg/Pro genotype had lower risk to develop NPC than those with Pro/Pro genotype (P<0.05). Collectively, we suggest that the p53 gene polymorphism may associate with NPC susceptibility in Thai population, particularly the Pro/Pro genotype carriers with age of >40 years. The detection of this p53 polymorphism may be a useful tool for screening of early stage and diagnosis of NPC.