Objective To investigate the prognostic value of optic nerve sheath diameter(ONSD)measured by critical care ultrasound combined with serum biomarkers[S100 calcium-binding protein β(S100β)and neuron-specific enolase(NSE)]in patients with severe traumatic brain injury.Methods A total of 103 adult severe traumatic brain injury patients admitted to the intensive care unit of this hospital from A-pril 1,2023,to April 1,2024 were enrolled.All patients underwent invasive intracranial pressure monitoring after admission,alongside bedside critical care ultrasound measurement of ONSD at 3 mm behind the globe and serum biomarker testing.Baseline data and Glasgow outcome scale(GOS)scores at 90 days after dis-charge were recorded.Patients were divided into the survival and the non-survival groups based on GOS scores.Receiver operating characteristic(ROC)curve analysis and area under the curve(AUC)were used to evaluate the predictive performance of ONSD and serum biomarkers for poor prognosis in severe traumatic brain injury patients.Results Ninety-six patients were ultimately included,with 52(54.1％)in the survival group and 44(45.9％)in the non-survival group.Significant differences were observed in blood glucose,Glas-gow coma scale(GCS)score,acute physiology and chronic health evaluation Ⅱ(APACHE Ⅱ)score,ONSD,NSE,and S100β levels(P＜0.05)between the two groups.Multivariate analysis identified ONSD(OR=4.962,95％CI:3.473-6.254),NSE(OR=2.704,95％CI:1.987-3.033),S100β(OR=2.983,95％CI:1.843-4.571),and APACHE Ⅱ score(OR=3.726,95％CI:2.837-4.592)as independent predictors of mortality in severe traumatic brain injury patients(P＜0.05).The combination of ONSD,NSE,and S100β yielded an AUC of 0.840 for predicting poor prognosis,with a specificity of 88.3％and sensitivity of 98.6％.Conclusion ONSD and serum brain injury biomarkers(NSE,S100β)are associated with in-hospital prognosis in severe traumatic brain injury patients.Their combined detection can effectively predict a poor outcome.