Introduction: Head injury recently replaced by the new term: traumatic brain injury (TBI) is a common cause of death worldwide and many researchers report it as a global health problem. The main cause of TBI is associated with various forms of violent, domestic, or accidental death. In these cases, an autopsy is mandatory to understand the immediate cause of death and its relationship to the TBI. Our study aimed to understand the general histopathological changes and expression of various immunohistochemical markers in TBI at medico-legal autopsies. Material and methods: Autopsies were performed on 20 cadavers whose cause of death was a traumatic brain injury and 20 cadavers with sudden deaths. The postmortem examination was performed by a forensic expert under the Virchow method. After labeling of brain tissues and fixation in formalin solution, they were transported to the histological department. The tissues were stained with hematoxylin and eosin (H&E) for histological assessment. Additional slices were taken for immunohistochemical examination. In our research, we used primary antibodies for GFAP, Ki67, and NeuN immunohistochemical markers. Results: The main histological changes in TBI were subarachnoid hemorrhages, perineuronal and perivascular edema, small foci of erythrocyte extravasation, and capillary stasis. From the immunohistochemical markers, GFAP showed some specific and interesting changes. Conclusions: Our data show that GFAP can serve as an immunohistochemical marker for TBI and its immunohistochemical staining changes can be a sequence of time-dependent events in TBI.