The Interleukin 1 family (IL-1 family) plays an important role in the immune and inflammatory responses in the human. Coronary artery disease (CAD) is a highly heritable inflammatory complex disease. The genetic role of IL-37, seventh member of IL-1 family in CAD has not been completely clarified. Our goal is to investigate whether SNP rs3811047 in the gene encoding cytokine IL-37 is associated with CAD in the Chinese Han Population. We performed the association analyses between rs3811047 and CAD in three-stage cohorts from three geographically different regions of China on a total of 2,460 individuals with CAD and 3,483 controls. Quantitative RT-PCR(qRT-PCR) analysis was performed to identify if IL-37 mRNA expression level was influenced by rs3811047. The minor allele A of rs3811047 was significantly associated with CAD in three independent cohorts in a genotypic model, with Padj=0.03 (OR=1.24) in the GeneID North Cohort, Padj=0.01 (OR=1.56) in the GeneID Central Cohort and Padj=5.00×10^-3 (OR=1.15) in the GeneID East Cohort. The association became more significant in the combined cohorts (P_obs=2.06×10^-6, P_adj=1.38×10^-5 under an additive model; P_obs=1.50×10^-6, P_adj=5.71×10^-5 under a dominant model; P_obs=6.06×10^-5, P_adj=1.15×10^-3 under a recessive model). Allele A of rs3811047 showed significant association with an decreased mRNA expression level IL-37 (n=168, P=3.78×10^-4). Based on the genetic evidence we have shown, the IL37 appears to have a genetic effect in the development of CAD, highlighting is a potential target for the prevention and treatment of CAD.