The tumor necrosis factor-alpha (TNF-alpha) promoter--238A/G polymorphism has been repeatedly associated with systemic lupus erythematosus (SLE), but findings are not consistent across studies. Our aim was to do a meta-analysis to assess the association between TNF-alpha promoter--238A/G polymorphism and SLE. Eleven published studies of this polymorphism with SLE in different ethnic groups were identified using a Medline search. Meta-analysis was performed for genotypes AA versus GG, GA versus GG, AA versus GG+GA, GA+AA versus GG, and A allele versus G allele in a fixed/random effect model. The overall odds ratio (OR) of the AA versus GG+GA genotypes was 3.46 (95% CI = 1.35-8.83, P = 0.01), and a similar result was found in Caucasian population (OR = 4.62, 95% CI = 1.20-17.80, P = 0.03); the overall OR of the AA versus GG genotypes was 3.36 (95% CI = 1.32-8.55, P = 0.01), and a similar result was found in Caucasian population (OR = 4.29, 95% CI = 1.11-16.53, P = 0.03); the OR of the GA versus GG genotypes was 0.48 (95% CI = 0.30-0.75, P = 0.001) in Caucasian population. In conclusion, this meta-analysis demonstrates the association between TNF-alpha promoter - 238A/G polymorphism and SLE, especially in Caucasian population.