Objective:To investigate the changes and clinical significance of serum S100β and neuron-specific enolase (NSE) levels of children with acute brain injury(ABI).Methods:100 children with ABI treated in the pediatric intensive care unit (PICU) of the Affiliated Hospital of Inner Mongolia Medical University from June 2019 to June 2020 were prospectively selected as the ABI group, and 30 normal children in the children′s health clinic of the hospital were selected as the control group. The serum S100β and NSE levels of all subjects was detected. According to the Glasgow Coma Scale (GCS), children with ABI were divided into severe brain injury group ( n=26), moderate brain injury group ( n=35) and mild brain injury group ( n=39). The prognosis of children with ABI after 3 months of treatment was evaluated according to the Glasgow prognosis scale (GOS) and they were divided into poor prognosis group ( n=26) and good prognosis group ( n=74). The relationship between serum S100β and NSE levels and the severity and prognosis of children with ABI was analyzed. Results:The serum S100β and NSE levels in the ABI group were significantly higher than those in the control group, and the serum S100β and NSE levels in children with ABI increased with the severity of injury and poor prognosis ( P<0.05). Pearson correlation analysis showed that serum S100β and NSE levels in children with ABI were positively correlated with GCS scores ( r=0.521, 0.643, P<0.05). Multiple logistic regression analysis showed that glucose(GLU) ( OR=1.631, 95% CI: 1.278-2.082), S100β ( OR=1.907, 95% CI: 1.558-5.877), NSE ( OR=2.896, 95% CI: 1.193-7.029) were independent prognostic factor in children with ABI ( P<0.05). Receiver operating characteristic (ROC) curve showed that the sensitivity, specificity and accuracy of serum S100β+ NSE [area under curve (AUC)=0.932, 95% CI: 0.875-0.969] in predicting the poor prognosis of children with ABI were higher than those of serum S100β(AUC=0.728, 95% CI: 0.643-0.803), NSE (AUC=0.808, 95% CI: 0.729-0.871) alone. Conclusions:The levels of serum S100β and NSE in children with ABI aresignificantly increased, which are closely related to the severity of the disease and prognosis. They can be used as predictors of poor prognosis in children with ABI. Combined detection can enhance the diagnostic value.