The latest data show that breast, prostate, lung and colorectal cancer are the four most frequent cancers in both sexes worldwide. A number of molecular epidemiological studies have been conducted to examine the association between TNF alpha -308G/A and the risk of those cancers. However the results have been inconclusive or inconsistent. We then performed a meta-analysis to derive a precise estimation of this association. We carried out a comprehensive search in Medline, EMBASE, OVID and Chinese Biomedical Literature Database for studies using related keywords. The inclusion criteria were (i) in English or Chinese; (ii) case-control study on this association; (iii) provide usable genotype frequencies; and (iv) sufficient published data for estimating an odds ratio (OR) with 95% confidence interval (CI). ORs and 95% CIs were calculated to assess the strength of this association under homozygote comparison (AA vs GG), heterozygote comparison (GA vs GG), dominant (AA/GA vs GG) and recessive (AA vs GA/GG) genetic model comparison. Thirty case-control studies with a total number of 16 507 cases and 19 749 controls were selected for analysis. Overall, no significant association was found between this polymorphism and the risk of total four cancers (GA vs GG: OR = 1.02, 95% CI = 0.91-1.14, P = 0.78). However, there was a significant association between this polymorphism and breast cancer risk in western populations (GA vs GG: OR = 0.91, 95% CI = 0.85-0.96, P = 0.002). This meta-analysis also revealed that this polymorphism was not associated with susceptibility to the other three cancers.