This study aimed to determine whether C20orf54 rs13042395 polymorphism modify the risk of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinomas (GCA) in common population. We conducted a systematic literature review and evaluated the quality of included studies based on Newcastle-Ottawa Scale (NOS). Pooled odds ratios (ORs) and corresponding 95% confidence intervals (95%CIs) were calculated to estimate the strengths of the associations. 9 articles (10 studies) were identified for synthesis analyses. Overall, the results indicated that the C20orf54 rs13042395 genotype was subtly decrease the risk of ESCC (T vs. C: OR = 0.95; 95%CI = 0.90-0.99; P = 0.02) and the rs13042395 polymorphism was associated with a decreased risk of GCA (T vs. C: OR = 0.95; 95%CI = 0.91-0.98; P < 0.01). The subsets were divided by smoking and drinking status, but none of the genetic comparisons reached statistical significance. Subgroup analysis was also stratified by body mass index (BMI), rs13042395 polymorphism was significantly associated with a subtly decreased cancer risk in under-weight group and normal group, but no association was observed in over-weight group. In conclusion, C20orf54 rs13042395 polymorphism was significantly associated with decreased ESCC and GCA risk especially for the subjects with under-weight or normal.