Background: p53 codon 72 polymorphism is associated with esophageal cancer (EC). Human papillomavirus (HPV) infection is considered as a risk factor of EC. However, the association of p53 codon 72 polymorphism with the risk of HPV-related EC remains inconsistent. Hence, we aimed to investigate the association between p53 codon 72 polymorphism and HPV-related EC risk through meta-analysis. Methods: All eligible studies published before November 1, 2015 were selected by searching PubMed, Embase, China National Knowledge Infrastructure (CNKI), and WanFang with the following key words: "p53", "HPV" or "human papillomavirus", and "esophageal cancer". Crude odds ratio (OR) with 95% confidence interval (CI) was used to assess the association. Statistical analyses were performed using Review Manager 5.2 and Stata/SE 12.0. Results: Twelve studies including 1682 HPV-related EC cases were included in this meta-analysis. p53 codon 72 genotypes were associated with HPV-related EC in an allelic model (Arg vs. Pro: OR=1.66, 95% CI=1.19-2.32, P=0.003), a homozygous model (ArgArg vs. ProPro: OR=1.73, 95% CI=1.26-2.37, P=0.0007), and a recessive model (ArgArg vs. ArgPro+ProPro: OR=2.39, 95% CI=1.45-3.94, P=0.0006). By contrast, significant association was not seen in a heterozygous model (ArgPro vs. ProPro: OR=0.85, 95% CI=0.61-1.19, P=0.33) and a dominant model (ArgArg+ArgPro vs. ProPro: OR=1.24, 95% CI=0.93-1.65, P=0.14). A greater association was observed in the subgroup of studies performing PCR-RFLP or real-time PCR for p53 genotyping and studies performing PCR to detect HPV status in allelic and recessive models. Conclusion: p53 codon 72 Arg homozygous genotype is a high risk factor of HPV-related EC. Individuals carrying ArgArg genotype exhibit an increased risk of EC with HPV infection.