Objective: To explore the predictive value of FIB, TBIL, and GDF-15 in the prognosis of cerebral atherosclerosis with acute stroke. Methods: 120 patients with ICAS combined with AIS who were admitted to our hospital from January 2022 to December 2024 were divided into ICAS combined with AIS group, and 120 patients with simple cerebral artery Congee and 120 healthy people were selected as simple ICAS group and healthy group respectively. Collect fasting venous blood samples from all patients on the first day of admission or in the early morning to measure FIB, TBIL, and GDF-15 levels. 120 patients with ICAS combined with AIS were followed up for 90 days. According to the MRS score, the patients were divided into two subgroups: good prognosis group (MRS ≤ 2 points, 75 cases) and poor prognosis group (MRS>2 points, 45 cases). The general data of the two groups were compared, and logistic regression model was used to analyze the prognostic factors of ICAS combined with AIS. ROC curves were established to analyze the predictive value of FIB, TBIL, and GDF-15 for the prognosis of ICAS combined with AIS. Results: The levels of FIB and GDF-15 in the ICAS combined with AIS group were higher than those in the simple ICAS group and the healthy group, while TBIL was lower than those in the simple ICAS group and the healthy group (P<0.05); The levels of hypertension, diabetes, TC, LDL-C, FIB, TBIL, GDF-15 in poor prognosis group and good prognosis group were significantly different (P<0.05); With poor prognosis as the dependent variable (Yes=1, No=0), the results showed that hypertension, diabetes, increased levels of LDL-C, FIB, GDF-15, and decreased TBIL were the risk factors for poor prognosis of CAS with AIS (P<0.05); By plotting ROC curves, the predictive value of FIB, TBIL, and GDF-15 for poor prognosis of ICAS combined with AIS was analyzed. The results showed that the combined prediction sensitivity and specificity of FIB, TBIL, and GDF-15 for poor prognosis of ICAS combined with AIS were due to their individual predictions. Conclusion: ICAS patients with AIS may experience abnormal increases in FIB and GDF-15 levels, as well as abnormal decreases in TBIL levels. Early combined detection of FIB, TBIL, and GDF-15 levels can predict the prognosis of patients.