Objective To explore the correlation of neutrophil to high-density lipoprotein cholesterol ratio (NHR) with the severity of coronary artery disease in patients attacked by non-ST segment elevation acute coronary syndrome (NSTE-ACS)．Methods A total of 168 consecutive patients with NSTE-ACS undergoing coronary angiography in North District of The First Affiliated Hospital of Anhui Medical University from August 2018 to April 2022 were enrolled for the retrospective study. The evaluation for the severity of coronary artery lesions in patients with NSTE-ACS was carried out taking Gensini score and the number of coronary artery lesions as reference. The enrolled patients were divided into low group (Gensini score＜45, n＝89) and high group (Gensini score ≥45, n＝79) based on the Gensini score, then into single-vessel and double-vessel coronary artery disease group (n＝87) and three-vessel or more coronary artery disease group (n＝81) according to the number of diseased coronary vessels. Clinical data between groups were compared. Multivariate binary logistic regression was performed to identify the independent risk factors of high Gensini score group and three-vessel or more coronary artery disease group in NSTE-ACS patients. Receiver operating characteristic (ROC) curve was plotted for assessing the predictive value of NHR on the severity of coronary artery disease in NSTE-ACS patients. Results The significantly increased NHR was displayed in Gensini high group and three-vessel or more coronary artery disease group (P＜0.05). The results of multivariate binary logistic regression analysis indicated NHR as an independent risk factor driving high Gensini score and three or more coronary vessel lesions in patients with NSTE-ACS (OR=1.702, 95% CI: 1.135～2.551, P=0.010; OR=1.312, 95% CI: 1.020～1.688, P=0.034). The area under the ROC curve of NHR predicting high Gensini score in NSTE-ACS patients was 0.668, with the best cut-off value of 6.043, the sensitivity of 37.2%, and the specificity of 89.9%. The area under the curve of NHR predicting the lesion of three or more coronary vessels in NSTE-ACS patients was 0.658, the best cut-off value was 4.334, the sensitivity of 65%, and the specificity of 62.1%. Conclusion NHR acts as an independent risk factor for the severity of coronary artery disease in patients with NSTE-ACS, exerting a robust predictive value for the severity of coronary artery disease in patients with NSTE-ACS