To investigate the correlation between high-density lipoprotein cholesterol (HDL-C) and cerebral tissue hypoperfusion in patients with symptomatic intracranial atherosclerotic stenosis (ICAS). Methods: A retrospective analysis was conducted on the clinical data of patients who received endovascular intervention for ischemic stroke caused by symptomatic unilateral internal carotid artery C4-7 segment or middle cerebral artery M1 segment stenosis (50%-99% ) at the Department of Neurology, Ordos City Central Hospital from January 2017 to December 2022. Patients were divided into a low perfusion group (penumbra volume ≥ 15 mL) and a non-low perfusion group (penumbra volume <15 mL) based on their computed tomography perfusion (CTP) imaging. Differences in clinical data between the two groups were compared, and significant indicators from univariate analysis were entered into multivariate binary logistic regression analysis. Significant indicators from the multivariate analysis were subjected to ROC curve analysis. Results: A total of 120 patients were included, of whom 48 (40%) had CTP low perfusion; intergroup difference analysis showed that the collateral circulation grade of the non-low perfusion group was significantly better than that of the low perfusion group (P<0.05), and the HDL-C level of the low perfusion group was significantly lower than that of the non-low perfusion group (P<0.05). Multivariate logistic regression analysis indicated that reduced HDL-C was an independent risk factor for cerebral tissue hypoperfusion in patients with symptomatic ICAS (OR=0.021, P= 0.035, 95%CI 0.001～0.756), with an optimal cutoff value of 1.02 mmol/L. At this point, the area under the ROC curve reached 0.759, P<0.05, sensitivity was 91.67%, specificity was 55.56%, and 95%CI was 0.569～ 0.896. Conclusion: The HDL-C level of the low perfusion group in patients with symptomatic ICAS was significantly lower than that of the non-low perfusion group, and reduced HDL-C was an independent risk factor for cerebral tissue hypoperfusion in patients with symptomatic ICAS.