Aims to explore the interaction between serum selenium level and CYP4F2 and CTRP9 gene polymorphisms in the development of coronary artery disease (CAD).A total of 200 cases of CAD were selected from the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Hubei, China, and 200 healthy subjects cases were served as controls. The polymorphism of CYP4F2 and CTRP9 gene was detected by Sanger sequencing, and the serum selenium level was measured by hydride generation atomic fluorescence spectrometry.The serum selenium level in the CAD group was significantly lower than that in the control group. The risk of CAD was decreased in the patients carrying the AA genotype in CYP4F2 rs3093135, while the frequency of the CC genotype of CTRP9 rs9553238 in CAD patients was higher than that in control subjects. Low serum selenium level and CTRP9 rs9553238 CC genotype play a positive role in the occurrence of CAD.The serum selenium level is negatively correlated with CAD. The polymorphism of the CYP4F2 rs3093135 and CTRP9 rs9553238 was significantly related to the susceptibility of CAD, and there is a synergistic effect between the serum selenium level and the CTRP9 rs9553238 CC genotype, which significantly increases the risk of CAD.