The reported results of the relationship between genetic polymorphisms of tumor necrosis factor (TNF)-α -238, -308 locus and ankylosing spondylitis (AS) susceptibility are not always consistent. This article aims to perform a meta-analysis to collect all the relevant studies to date to further clarify the relationship between those genetic polymorphisms and AS.A computer search was carried out up to September 2011 for literature pertaining to AS and TNF-α polymorphisms.Twenty-two articles were included, with 2,506 cases of AS and 3,023 normal controls. We searched for genotypes A allele vs. G allele, AA vs. GG + GA, and GA + AA vs. GG in a fixed/random-effects model. The effect summary odds ratios (ORs) and 95 % confidence intervals (CIs) were obtained, which shows there was no association between genetic polymorphisms and AS. As the heterogeneity was observed, in a subgroup analysis by ethnicity, the degree of risk of two genes with AS susceptibility was similar in populations of European and Asian origin. For the human leukocyte antigen (HLA)-B27+ population, results were not statistically significant.ORs of various comparisons indicate that there is no association between TNF-α -238, -308 polymorphisms and AS susceptibility in the overall population and in the subgroup of Asian and non-Asian descent.