Objectives/ Hypothesis An important tumor suppressor gene, p53, plays a role in the regulation of cell progression and prevention of carcinogenesis. Mutated p53 is related to cell progression and malignancy. We aimed to evaluate the association between nasopharyngeal carcinoma and p53 polymorphism. Study Design Case control study. Methods All individuals were divided into two groups: nasopharyngeal carcinoma (n = 50) and non-nasopharyngeal carcinoma groups (n = 59). Their p53 codon 72 polymorphisms (arginine [Arg] homozygotes, heterozygotes, proline [Pro] homozygotes) were detected by polymerase chain reaction. Associations between nasopharyngeal carcinoma and p53 polymorphism were evaluated. Results Distributions of various p53 polymorphisms significantly differed between the two groups. We noted a dominant presentation of Pro homozygotes in the nasopharyngeal carcinoma population over that in the non-nasopharyngeal carcinoma population. Proportions of Pro homozygotes and heterozygotes and Arg homozygotes were 32%, 28%, and 40% in the nasopharyngeal carcinoma population and were 13.5%, 44.1%, and 42.4% in the non-nasopharyngeal carcinoma population, respectively. Conclusions An association exists between nasopharyngeal carcinoma and p53 codon 72 polymorphism. The p53 Pro homozygotes are to a higher risk of development of nasopharyngeal carcinoma.