Aim To investigate the changes of serum neurofilament-light (NF-L), thrombospondin-1 (TSP-1) levels in patients with craniocerebral injury,and analyze their predictive value for the prognosis of patients with craniocerebral injury. Methods 106 craniocerebral injury patients were selected,according to Fisher CT grade the patients were divided into 1 ~ 2 grade group(47 cases) and 3 ~ 4 grade group(59 cases), according to the Glasgow coma scale (GCS) the patients were divided into light coma group(12~15 points, 34 cases), medium coma group (7~11 points, 49 cases), and heavy coma group(＜7 points,23 cases), according to the injury after 30 days Glasgow outcome scale (GOS) the patients were divided into poor prognosis group(GOS scores 1~3,8 cases) and good prognosis group(GOS scores 4~5,8 cases). Another 103 healthy volunteers (control group) were selected. Serum NF-L and TSP-1 levels were detected by enzyme linked immunosorbent assay. Spearman rank correlation analysis was used to analyze the correlation between serum NF-L, TSP-1 level and Fisher CT grade, GCS scores, GOS scores in craniocervical injury patients. Logistic regression analysis was used to analyze the risk factors affecting the prognosis of patients with craniocerebral injury. The receiver operating characteristic (ROC) curve was used to analyze the value of serum NF-L and TSP-1 levels in predicting the prognosis of patients with craniocerebral injury. Results Serum NF-L, TSP-1 levels in craniocerebral injury group were higher than control group(P＜0.05); The serum NF-L,TSP-1 levels in Fisher CT 3~4 grade group were higher than that in 1 ~ 2 grade group(P＜0.05); And the serum NF-L,TSP-1 levels in heavy coma group were higher than medium coma group and light coma group(P＜0.05); The serum NF-L,TSP-1 levels in medium coma group were higher than light coma group(P＜0.05); The serum NF-L and TSP-1 levels in the poor prognosis group were higher than those in the good prognosis group(P＜0.05). Spearman rank correlation analysis showed that serum NF-L and TSP-1 levels were positively correlated with Fisher CT grade(r_s=0.2,0.593, P＜0.05), and negatively correlated with GCS score and GOS score(r_s=－0.589, －0.693; －0.629, －0.617, P＜0.05). Logistic regression analysis showed that Fisher CT grade, GCS scores, NF-L, and TSP-1 were correlated with the prognosis of patients with craniocerebral injury (P＜0.01). ROC curve analysis showed that the area under the curve (AUC) of serum NF-L and TSP-1 to predict the prognosis of patients with craniocerebral injury were 0.3,0.836 respectively, and the AUC combined with NF-L and TSP-1 was 0.937, which was higher than that of NF-L and TSP-1 alone(P＜0.05). Conclusion Serum NF-L and TSP-1 are significantly increased in patients with craniocerebral injury, and the NF-L and TSP-1 levels are closely related to the severity and prognosis of craniocerebral injury, and can be used as a reference index for prognosis assessment.