Background: Interleukin (IL)-37, also called ILI F7, is a natural inhibitor of inflammatory and immune responses. It is involved in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the role ofJLiF7 gene polymorphism in RA susceptibility in a large cohort of patients. Methods: Five selected single-nucleotide polymorphisms inILIF7 genes (rs2723186, rs3811046, rs4241122, rs4364030, and rs4392270) were genotyped by TaqManAllelic Discrimination in Northern Chinese Han population. The allele and the genotype were compared between patients with RA and healthy controls. Association analyses were performed on the entire data set and on different RA subsets based on the status of the anti-cyclic citrullinated peptide antibody and the rheumatoid factor by logistic regression, adjusting for age and gender. Results: Trend associations were detected between rs2723186, rs4241122, rs4392270, and RA in Stage 1 (160 patients with RA; 252 healthy controls). Further validation in Stage II comprised 730 unrelated patients with RA (mean age: 54.9 +/- 12.6 years; 81.6% females) and 778 unrelated healthy individuals (mean age: 53.5 +/- 15.7 years; 79.5% females). No significant differences in the distributions of alleles and genotypes were observed between the case and control groups in both the entire set and the different RA subsets. Disease activity and age of RA onset were also not associated with genotype distributions. Conclusion: ILIF7 gene polymorphism does not significantly influence RA susceptibility in the Northern Chinese Han population.