Penetrating brain injury caused by a nail is an extremely rare neurosurgical emergency that poses a challenge for neurosurgeons. Nail entering the brain from the orbit and lodging within the cranial cavity is even more unusual. A 53-year-old male was found unconscious at a construction site, and brain CT revealed not only the presence of a nail beneath the inner table of the parietal bone, but also traumatic intracerebral hematoma. Consequently, accurate localization of the nail and hematoma was mandatory for surgical plan. During surgical planning, computational model reconstruction and trajectory calculation were completed using preoperative CT in 3D Slicer. Under the guidance of a head-mounted mixed-reality holographic computer, the neurosurgeon was able to visualize and interact with the hologram of the surgical plan, and intraoperative findings demonstrated that our low-cost portable wearable mixed-reality holographic navigation assisted precise localization of the nail and intracerebral hematoma, assuring less injury to the already compromised brain. After the surgery, the patient could obey commands, and postoperative imaging ruled out the possibility of brain abscess during follow-up. To the best of our knowledge, this is the first report on using a low-cost wearable mixed-reality holographic navigation to guide the management of penetrating intracranial injury caused by a nail. © 2021, Society for Imaging Informatics in Medicine.