Objective Through the combined detection method,we tried to find more sensitive biomarkers for the diagnosis of acute TBI,which might provide the exact diagnosis,treatment and monitoring indicators for the clinic.Methods A total of 156 patients with acute TBI admitted to the Emergency Traumatic Center of Yan'an Hospital of Kunming from October 2022 to June 2023 were collected and included the normal and fracture control groups.Peripheral blood samples of the enrolled patients were collected and monitored,S100β and IL-6 were tested and clinical data such as hs-CRP was collected immediately upon admission,then statistical analysisanalysis was conducted.Results Peripheral blood in patients with acute TBI,The levels of S100β,IL-6 and hs-CRP significantly increased,and the area under the ROC curve for diagnosing acute TBI was 0.944,0.915,and 0.897.The combined detection of the three indicators showed an area under the ROC curve of up to 0.975.Person correlation analysis found a positive correlation between the three indicators,especially S100β with IL-6,The correlation coefficient between them is 0.715.Binary logistic regression analysis found that S100β,IL-6 and hs-CRP are independent risk factors for acute TBI.Conclusions The combined detection of S100β,IL-6 and hs-CRP can effectively improve the sensitivity of acute TBI diagnosis.The mutual promotion of S100β and IL-6 may aggravate the secondary craniocerebral injury caused by inflammatory mechanism,and early targeted treatment may improve the prognosis.