Tumor necrosis factor-alpha (TNF-α) has been regarded as a candidate gene for Crohn's disease (CD) based on its inflammatory function in immune reaction and the clinical effectiveness of anti-TNF-α therapy. However, studies to date have reported inconsistent findings for the association between TNF-α and CD. The PubMed, EMBASE, and Medline databases were systematically reviewed from all English language publications up to April, 2011. A total of twenty-nine studies concerning the association between CD and the TNF-α promoter polymorphisms of -308G/A, -857C/T and -238G/A were identified, among of them only twenty-three studies match the inclusion criteria (including 3,843 cases and 6,260 controls) and were selected for the statistical test. We found that neither the G allele of -308G/A (OR 1.02, 95% CI 0.87-1.19, P = 0.84), C allele of -857C/T (OR 0.97, 95% CI 0.86-1.09, P = 0.57) and G allele of -238G/A (OR 0.91, 95% CI 0.70-1.18, P = 0.48), and nor their GG (OR 1.05, 95% CI 0.88-1.25, P = 0.59), CC (OR 0.98, 95% CI 0.86-1.12, P = 0.76) and GG (OR 0.92, 95% CI 0.70-1.21, P = 0.55) genotypes were associated with CD susceptibility, respectively. Our meta-analysis demonstrates that three promoter polymorphisms of TNF-α above may not confer susceptibility to CD.