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Studies investigating the association between interleukin (IL)-4 gene promoter -590C/T (rs2243250) polymorphism and autoimmune diseases report conflicting results. To derive a more precise estimation of the relationship, a meta-analysis was performed.A systematic literature search was conducted to identify relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to estimate the strength of association.A total of 6001 cases and 6788 controls from 24 studies were analysed. Significant association of the C allele of IL-4 rs2243250 polymorphism with rheumatoid arthritis (RA) was detected (odds ratio (OR) = 0.696, 95% confidence interval (CI) = 0.601–0.807). Stratification by ethnicity indicated an association between the IL-4 rs2243250 polymorphism and RA in Caucasians. Furthermore, the overall ORs of the associations between the C allele and multiple scleorosis (MS) were 1.340 (95% CI = 1.102–1.630). However, we failed to reveal any association between IL-4 rs2243250 polymorphism and systemic lupus erythematosus (SLE), type 1 diabetes (T1D) or Graves' disease (GD).The present study suggests that the IL-4 rs2243250 polymorphism might be associated with genetic susceptibility to autoimmune diseases, including RA and MS.