Circular RNAs (circRNAs) have been reported to aberrantly express in coronary artery disease (CAD). Due to their special structures, circRNAs have the potential to be specific and stable markers. We conducted this study to explore circZNF609's function in atherosclerosis and to evaluate its predictive values for CAD. About 330 CAD patients and 209 controls were enrolled and the expression of circZNF609 in peripheral blood leukocytes (PBLs) was detected by quantitative real time polymerase chain reaction (RT-PCR). Spearman correlation, multivariate regression, multivariate logistic regression and receiver operating characteristic curve (ROC) were performed. Moreover, circZNF609 was overexpressed in mice macrophage RAW264.7 to investigate its influence on inflammatory cytokines. Finally, bioinformatics analysis was executed to excavate the potential downstream pathway of circZNF609. The expression level of circZNF609 in PBLs of CAD patients was significantly decreased compared with the controls (the fold changes of 0.4133, P<0.0001). The logistic regression analysis showed that decreased circZNF609 expressions were independently associated with increased risks of CAD. The area under the ROC curve was 0.761 (95% CI: 0.721-0.800, P<0.0001). Furthermore, the circZNF609 expression level was correlated with C-reactive protein (r=-0.138, P=0.026) and lymphocyte counts (r=0.16, P=0.01). After overexpression of circZNF609 in RAW264.7 cells, the expression level of IL-6 (P<0.001) and TNF-α (P<0.01) were significantly decreased and IL-10 was significantly increased (P<0.001). Bioinformatics analysis suggested that the abnormal expression of circZNF609 might probably sponge miRNA to modulate the inflammation cytokines. CircRNA ZNF609 played an anti-inflammatory role and was an independent protective factor for CAD. It represented a moderate diagnostic value and might provide a new therapeutic target for CAD. 2020 Annals of Translational Medicine. All rights reserved.