Traumatic brain injury (TBI) affects approximately 10 million people annually worldwide.Depression is one of the most prevalent and disabling psychiatric disorders in people with TBI.Depression after TBI is closely related with social and psychological factors and the hypothalamic-pituitary-adrenal (HPA) axis dysfunction.However, there is a lack of evidence regarding effective treatment depression approaches.In this study we investigated the relationship of depression degree of TBI patients with the severity and progress of TBI.We also investigated the therapeutic effects of anti-depression drugs in combination with psychotherapeutic and rehabilitation interventions and hormone supplement to modulate TBI patients with depression.A total of 64 patients with depression following closed TBI were recruited for the study.We found that there is no relationship between the severity of depression and the severity and progression of TBI.Combination of hormone administration with psychotherapeutic and anti-depression drug treatment significantly improved depression functional outcome after TBI.Conclusion: Depression degree after TBI is not related with the severity and progression of TBI.Combination of hormone supplements with psychotherapeutic and anti-depression drug treatment significantly improves functional outcome in TBI depression patients.