Objective：To explore the relationship between the levels of S100 calcium binding protein，homocysteine(homocysteine， Hcy)and neuron specific enolase(neuronspecificenolase，NSE)in peripheral blood and the absorption of intracranial hematoma and cognitive function in patients with traumatic craniocerebral injury. Methods：A retrospective analysis was made on 74 patients with traumatic craniocerebral injury treated in our hospital from January 2018 to December 2020 as the observation group，and 75 healthy persons who underwent physical examination in our hospital in the same period were selected as the control group. The levels of S100 calcium binding protein，Hcy and NSE in peripheral blood of the two groups were compared. According to the absorption of hematoma and the occurrence of cognitive impairment，the observation group was divided into good absorption group，poor absorption group or cognitive impairment group and non - cognitive impairment group. The levels of S100 calcium binding protein，Hcy and NSE were compared among the groups. The correlation of hematoma absorption and cognitive function with the levels of S100 calcium binding protein，Hcy and NSE in peripheral blood was analyzed. Results：The levels of S100 calcium binding protein，Hcy and NSE in the observation group were significantly higher than those in the control group，the serum levels of S100 calcium binding protein，Hcy and NSE in the good absorption group were significantly lower than those in the malabsorption group，and the serum levels of S100 calcium binding protein，Hcy and NSE were positively correlated and negatively correlated with the absorption level of hematoma，that is，the better the absorption of hematoma，the lower the serum index. The levels of serum S100 calcium binding protein，Hcy and NSE in patients with cognitive impairment were significantly higher than those without cognitive impairment，and there was a positive correlation between cognitive impairment and serum levels of S100 calcium binding protein，Hcy and NSE(P ＜ 0.05). Conclusion： The hematoma absorption and cognitive function of patients with traumatic craniocerebral injury are significantly correlated with the levels of S100 calcium binding protein，Hcy and NSE in peripheral blood，which is helpful for the clinical diagnosis and treatment of the disease.