Overexpression of p53, a tumor suppressor protein, was reported in oral and pharyngeal squamous cell carcinoma in Thai patients. The polymorphism in p53 gene exon 4 codon 72 was reported in oral cancer patients from southern part of Thailand with no correlation to any risk factors. Since the genetic diversity may affect the susceptibility of an individual to oral cancer, patients from other parts of Thailand may differ in the association of cancer risks. Objectives: The purpose of this study was to analyze the correlation between p53 codon 72 polymorphism in oral SCC patients from northeastern and central part of Thailand and clinicopathologic features and etiologic factors. Methods: The p53 codon 72 polymorphism was determined in 28 oral SCC patients using PCR-RFLP technique. The correlation between clinicopathologic features of the patients and p53 polymorphism was analyzed using Chi Square test. Results: The PCR-RFLP analysis of 28 oral squmous cell carcinoma cases showed different in frequencies in three genotypes. The highest frequency was 46.5% in Arg/Pro genotype, while the frequencies of Arg/Arg and Pro/Pro genotype were 21.5% and 32% respectively. No significant association between p53 genotype frequencies and oral cancer etiologic factors was observed. There was also no significant association between p53 polymorphism and clinicopathological features such as age, sex, stage of the disease, and grade of tumor differentiation. However histopathology of an Arg/Arg genotype individual tended to develop to well differentiated tumor (OR= 6.25), while non-invasive node individual was likely to have Pro/Pro genotype (OR= 3.5). Conclusions: p53 codon 72 polymorphism may not associated with clinicopathologic features and risk factors in Thai oral squamous cell carcinoma. Individual with an Arg/Arg genotype tends to develop low aggressive type of tumor, while Pro/Pro genotype may provide some protection against tumor invasion. This work was supported by Faculty of Dentistry, Mahidol University, Thailand.