In this study, we examine the association of single nucleotide polymorphisms (SNPs) of the human ATP binding cassette transporter G1 (ABCG1) gene with atherosclerotic coronary artery disease (CAD) in a Chinese Han population.1021 patients with CAD and 1013 unaffected control subjects were enrolled. PCR-based ligation detection reaction (PCR-LDR) method was used to genotype four SNPs of ABCG1, three (rs2234714, rs2234715 and rs57137919) in the promoter region and one (rs1044317) in the 3′-untranslated region (UTR).The human ABCG1 −367G>A polymorphism (rs57137919) showed a significantly decreased risk for CAD and myocardial infarction (MI) in a dominant model (adjusted OR=0.73, p=0.033 for CAD, and adjusted OR=0.65, p=0.014 for MI, respectively). The rs57137919 also showed an association with angiographic severity of CAD (multi-vessel vs. single-vessel CAD, adjusted OR=0.40, p=0.005). The findings were further supported by luciferase reporter assay, in which the polymorphism impaired reporter gene expression. The ABCG1 −768G>A polymorphism (rs2234714) showed an association with CAD in a recessive model (adjusted OR=0.64, p=0.015), but did not demonstrate a functional influence on reporter gene expression in the luciferase reporter assay.The SNP rs57137919 in the ABCG1 promoter region is functionally associated with a reduced risk of CAD in a Chinese Han population.