Objective: To study the association between tumor suppressor p53 codon 72 polymorphism and the susceptibility of oral cancer by Meta-analysis. Methods: We conducted a systematic electronic search of the literatures about p53 codon 72 polymorphism and the susceptibility of oral cancer on VIP, CNKI, Wanfang, CBM, PubMed, Embase and Web of Science. Odds ratios (OR) with 95% confidence interval (95%CI) acted as the effect index to estimated Meta-analysis which performed by STATA14 and RevMan5 software, as well as the publication bias and sensitivity analysis were identified. Results: A total of 16 case-control studies with 2 317 oral cancer patients and 2 933 normal controls were included in the current Meta-analysis. The results demonstrated that the association between p53 codon 72 polymorphism and oral cancer risk were not statistically significant (Pro vs Arg OR=1.03, 95%CI: 0.887–1.195; ArgPro + ProPro vs ArgArg OR=0.957, 95%CI: 0.847–1.081; ProPro vs ArgArg + ArgPro OR=1.082, 95%CI: 0.835–1.401; ProPro vs ArgArg OR=1.059, 95%CI: 0.783–1.433; ArgPro vs ArgArg OR=0.946, 95%CI: 0.831–1.076; ArgArg + ProPro vs ArgPro OR=0.943, 95%CI: 0.842–1.055). Subgroup analysis based on ethnicity and source of normal control population further identified the p53 codon 72 polymorphism was not linked to oral cancer risk. Conclusion: The polymorphism of p53 codon 72 polymorphism is not directly associated with the susceptibility of oral cancer, which maybe not an independent factor of the susceptibility of oral cancer.