Aim To investigate the serum levels of thrombin-antithrombin complex (TAT), tissue type plasminogen activator-inhibitor complex (t-PAIC) and thrombomodulin (TM) in patients with intracranial atherosclerotic stenosis (ICAS), and their correlations with the degree of stenosis. Methods A total of 196 ICAS patients (ICAS group) who underwent treatment in Cangzhou People's Hospital from January 2021 to February 2023 were enrolled as research subjects. Based on the degree of vascular stenosis, they were separated into three groups:mild group (n＝78), moderate group (n＝64), and severe group (n＝54). A group of 196 healthy outpatient with similar clinical basic data to ICAS patients was selected as controls. The serum levels of TAT, t-PAIC, and TM in each group were compared; Spearman method was applied to analyze the correlation between serum levels of TAT, t-PAIC, TM and stenosis severity in ICAS patients; Multivariate Logistic regression was applied to analyze the influencing factors of severe stenosis in ICAS patients; ROC curve was applied to analyze the predictive value of serum TAT, t-PAIC, TM and total cholesterol (TC) levels for severe stenosis in ICAS patients. Results Compared with the control group, the serum levels of TAT, t-PAIC, and TM were significantly increased in the ICAS group (P＜0.05); the levels of serum TAT, t-PAIC, TM, and TC in the mild, moderate, and severe groups increased accordingly (P＜0.05). Spearman analysis showed that the serum levels of TAT, t-PAIC, and TM in ICAS patients were positively correlated with the degree of stenosis (r＝0.4,0.5,0.628; all P＜0.05). Multivariate Logistic regression analysis showed that TAT, t-PAIC, TM, and TC were independent risk factors for severe stenosis in ICAS patients (P＜0.05). The ROC curve showed that the AUC of severe stenosis in ICAS patients predicted by combination of TAT, t-PAIC, TM, and TC was 0.927, with a sensitivity of 83.33% and a specificity of 86.62%, which was superior to the independent prediction of TAT, t-PAIC, TM and TC(Z_combined detection-TAT=4.617, Z_combined detection-t-PAIC=4.024, Z_combined detection-TM=4.004, Z_combined detection-TC=7.078, all P＝0.000). Conclusion The serum levels of TAT, t-PAIC, and TM in the ICAS group were significantly increased, and were positively correlated with the severity of stenosis. The combination of the three and TC has a high predictive value for the occurrence of severe stenosis in ICAS patients.