Serum neuritin and neuron-specific enolase (NSE) have predictive value for the prognosis of patients with combined traumatic brain injury (TBI) and spinal cord injury (SCI). Studying their predictive effects has positive value for disease control and treatment. Sixty patients with combined TBI and SCI were recruited and rolled into three groups according to prognosis: Group I (n=42, favorable prognosis), Group II (n=11, poor prognosis), and Group III (n=7, death). Clinical indicators were compared between the groups, and the predictive value of different indicators for prognosis was analyzed. NSE and serum neuritin levels were considerably higher in Groups II and III than in Group I (P<0.05). Multivariate logistic regression analysis showed that hypotension, NSE, serum neuritin, S100β, and combined injuries to other organs were associated with poor prognosis in patients with combined TBI and SCI. The combination of NSE and neuritin had considerably higher sensitivity (Sen), specificity (Spe), and accuracy (Acc) in predicting prognosis (P<0.05). Serum neuritin and NSE have favorable predictive value for the prognosis of patients with combined TBI and SCI. They can be actively promoted in clinical practice