Inflammation and lipid signaling are involved in the pathogenesis and progression of coronary artery disease (CAD). We proposed that high-sensitivity C-reactive proteins, as a marker of the pro-inflammatory state, and high-density lipoprotein cholesterol (HDL-C), as an anti-atherosclerosis component, should be integrated into a single novel biomarker. Our work was conducted to discuss and compare the predictive ability of the high-sensitivity C-reactive protein to high-density lipoprotein cholesterol ratio (CHR) with other existing indices, for example, neutrophil high-density lipoprotein ratio (NHR) and neutrophil lymphocyte ratio (NLR), in the severity of CAD patients.Based on the results of coronary angiography, patients were divided into the CAD+ group, CAD- group, and control group. The relationship between various serum markers and the severity of coronary artery disease was examined via Spearman's correlation analysis. Logistic regression analysis was conducted to identify the influencing factors of the coronary artery disease severity.This study included 420 patients. The Gensini score was positively correlated with CHR. Multiple regression analysis revealed that the CHR was significantly associated with CAD. CHR is an independent predictor of CAD. The receiver operating characteristic (ROC) analysis provided a cut-off value of 1.17 for CHR to predict CAD, with a specificity of 86.7%, Yoden index of 0.264, and area under the ROC curve of 0.662 (95% confidence intervals 0.606-0.719, P < 0.001). At the same time, the area under the ROC curve of the NHR was 0.652, and that of the NLR was 0.579. The results of the DeLong test indicated that the area under the ROC curve of the CHR was larger than that of the NLR (P = 0.0306). This suggests that the CHR as a predictor of CAD has better diagnostic performance than the NLR.CHR was not only closely related to the presence and severity of CAD but also an independent predictor of severe CAD.