The aim of the present study was to evaluate the relationship between tumor necrosis factor-Ξ± (TNF-Ξ±) and the development of gastric cancer, and to investigate whether it can be used as a biological marker for gastric cancer. In the current study, a new meta-analysis was performed to assess the association between TNF-Ξ± gene polymorphisms and gastric cancer susceptibility. Subgroup analyses based on ethnicity, control population source and non-cardia cancers were also conducted. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. TNF-Ξ± 308 polymorphisms indicated a significant relationship with gastric cancer risk among a normal population [GA/AA vs. GG; 1.17 (1.10β1.23)]. In analysis stratified by ethnicity, TNF-Ξ± 238 displayed an association with gastric cancer risk in eastern populations [GA/AA vs. GG: 1.24 (1.02β1.50)], but not in western populations [GA/AA vs. GG: 0.96 (0.79β1.18)]. The overall ORs (95% CIs) for TNF-Ξ± 857, TNF-Ξ± 1031 and TNF-Ξ± 863 were 1.13 (1.04β1.24), 0.94 (0.85β1.05) and 0.89 (0.78β1.02), respectively, under dominant genetic model comparison. Among the above three SNPs, only TNF-Ξ± 857 was robustly associated with gastric cancer inclination, and this association remained consistently robust when limited to non-cardia gastric cancers [GA/AA vs. GG: 1.16 (1.03β1.31)]. TNF-Ξ± 308 and TNF-Ξ± 857 genotypes were potential risk factors of statistical significance in gastric cancer, and TNF-Ξ± 238 indicated to be significantly associated with gastric cancer risk only in eastern populations. TNF-Ξ± 1031 and TNF-Ξ± 863 were not significantly associated with gastric cancer risk.