Background: High-risk Human Papillomavirus infections, and polymorphism of the p53 gene, have been implicated in oral potentially malignant disorders. The present study determines whether the polymorphism at codon 72 of the p53 gene and the presence of HPV-16/18 strains are associated with OLP patients. Materials and methods: The biopsy specimens were obtained from 250 OLP individuals. The samples were processed for HPV-DNA analysis and polymorphism of the p53 gene using PCR. Data were analyzed by applying the Chi-square test. Results: There were 103 positive HPV sample specimens with 34 males and 69 females which were shown to be statistically significant (p<0.001). Arg/Arg, Pro/Pro, and Arg/Pro were found in 19.4%, 31.1%, and 50% of HPV-positive cases of OLP, respectively, compared to 17%, 47%, and 36% of HPV-negative samples, which were found to be statistically significant between the two groups. The Arginine allele (44%) was more prevalent in HPV-associated OLP than in HPV-negative OLP cases (35%) which was found to be statistically significant between the groups. Conclusion: The results of the current study relate to the premalignant potential of OLP based on the occurrence of codon 72 of the p53 gene polymorphism in HPV-associated OLP patients in terms of genotype and allele.