Objective To investigate the clinical significance of serum S100 calcium binding protein(S100 A4)and S100A12 in patients with severe traumatic brain injury(sTBI).Methods A total of 147 sTBI pa-tients admitted to Handan Central Hospital from March 2021 to March 2023 were selected as the sTBI group,and 50 healthy subjects who underwent physical examination in Handan Central Hospital during the same pe-riod were selected as the control group.The correlation between S100A4,S100A12 levels and brain injury markers and the influencing factors of early death in sTBI patients were analyzed,and the predictive value of serum S100A4 and S100A12 for early death in sTBI patients was studied.Results The serum levels of S100A4,S100A12,myelin basic protein(MBP),S100B and neuron specific enolase(NSE)in sTBI group were significantly higher than those in control group(P＜0.05).The serum levels of S100A4 and S100A12 were positively correlated with MBP,NSE and S100B in sTBI patients(P＜0.05).Multivariate Logistic regression analysis showed that decreased Glasgow coma scale(GCS)score on admission and increased serum levels of S100A4,S100A12,MBP,NSE and S100B were risk factors for early death in sTBI patients(P＜0.05).Receiv-er operating characteristic curve showed that the combination of serum S100A4 and S100A12 with GCS score,MBP,NSE and S100B was superior to any single detection in predicting early death in sTBI patients.Conclu-sion The serum levels of S100A4 and S100A12 are increased in sTBI patients,which are related to the aggra-vations of brain injury and early death.The combined detection of S100A4 and S100A12 has a good predictive value for early death in sTBI patients.