Tumor necrosis factor-α (TNF-α) is an immunoregulatory cytokine involved in B- and T-cell function, and also plays an important role in inflammation and cancer. TNF-α-308G>A has been associated with constitutively elevated TNF-α expression. Several studies have reported the association between the TNF-α-308G>A polymorphism and non-Hodgkin lymphomas (NHL) risk, however, results are still inconsistent. To solve these conflicts, we conducted the first meta-analysis to assess the effect of TNF-α-308G>A polymorphism on the risk of NHL and various subtypes (additive model) including 10,619 cases and 12,977 controls in Caucasian and Asian populations. Our meta-analysis indicated that TNF-α-308G>A polymorphism is not associated with NHL risk when pooling all studies together (OR=1.06, 95% CI: 0.92-1.23, p=0.413). In stratified analyses, we found TNF-α-308A allele was significantly associated with higher risk of NHL, B-cell lymphomas (BCL), T-cell lymphomas (TCL) and diffuse large B-cell lymphomas (DLBCL) in Caucasians (OR=1.22, 95% CI: 1.06-1.40, p=0.007; OR=1.18, 95% CI: 1.03-1.34, p=0.014; OR=1.20, 95% CI: 1.01-1.42, p=0.040; OR=1.21, 95% CI: 1.11-1.32, p<0.001, respectively). Interestingly, it was associated with decreased risk of NHL, BCL and DLBCL in Asians (OR=0.75, 95% CI: 0.66-0.86, p<0.001; OR=0.70, 95% CI: 0.52-0.94, p=0.018; OR=0.70, 95% CI: 0.57-0.86, p=0.001). These findings also suggest TNF-α might play a distinct role in pathogenesis of NHL in different populations.