Traumatic brain injury (TBI) has both high morbidity and mortality rates and can negatively influence physical and mental health, while also causing extreme burden to both individual and society. Hitherto, there is no effective treatment for TBI because of the complexity of the brain anatomy and physiology. Currently, management strategies mainly focus on controlling inflammation after TBI. Tumor necrotizing factor alpha (TNF-α) plays a crucial role in neuroinflammation post-TBI. TNF-α acts as the initiator of downstream inflammatory signaling pathways, and its activation can trigger a series of inflammatory reactions. Infliximab is a monoclonal anti-TNF-α antibody that reduces inflammation. Herein, we review the latest findings pertaining to the role of TNF-α and infliximab in TBI. We seek to present a comprehensive clinical application prospect of infliximab in TBI and, thus, discuss potential strategies of infliximab in treating TBI.