Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in children and adults throughout the world. It is urgent to ameliorate TBI damage and reduce the disability and case-fatality rate. Stem cell therapy is another medical revolution after drug and surgical medication. Mesenchymal stem cells (MSCs) are a class of cells with significant self-renewal and multi-lineage differentiation properties and be favorable for the treatment of various diseases and injuries, it could be envisioned that MSCs transplantation may be a promising treatment for TBI. Currently, stem cell therapy has shown promising effects in the treatment of many diseases. In this article, we will review the characteristics of MSCs, MSCs for neuronal function restoration, the properties of immune-modulatory of MSCs, and the anti-apoptotic effects of MSCs, the angiogenesis effect of MSCs,and the safety issues in MSCs therapy in TBI.