The TP53 Arg72Pro polymorphism has been investigated as a potential genetic hallmark of esophageal cancer, but studies investigating the association between the TP53 Arg72Pro polymorphism and esophageal cancer risk have reported conflicting results. A meta-analysis was conducted to reach a conclusion on such a possible association. Computer searches of the literature were conducted in Pubmed and Embase databases and 11 published case–control studies were finally included, involving a total of 2294 esophageal cancer cases and 4034 controls. When all 11 studies were pooled into the analysis, an increased esophageal cancer risk was significantly associated with the Pro variant of TP53 Arg72Pro in three genetic comparison models [odds ratio (OR)Pro vs. Arg=1.21, 95% confidence interval (CI): 1.05–1.39, POR=0.009; ORDominant genetic model=1.22, 95% CI: 1.09–1.37, POR=0.001; ORHomozygote model=1.40, 95% CI: 1.05–1.87, POR=0.024]. In subgroup analyses based on pathological type, the Pro variant was significantly associated with an increased esophageal squamous cell carcinoma (ESCC) risk in all four genetic comparison models (ORPro vs. Arg=1.26, 95% CI: 1.08–1.47, POR=0.003; OR Recessive genetic model=1.42, 95% CI: 1.07–1.88, POR=0.015; ORDominant genetic model=1.25, 95% CI: 1.10–1.42, POR=0.001; ORHomozygote model=1.55, 95% CI: 1.14–2.10, POR=0.005), whereas the association between TP53 Arg72Pro polymorphism and esophageal adenocarcinoma risk was still uncertain owing to the limited studies included in this meta-analysis. In addition, the association between TP53 Arg72Pro polymorphism and ESCC risk was also significant in Asians. These results suggest that the Pro variant of TP53 Arg72Pro is an important genetic hallmark contributing to ESCC risk.