OBJECTIVE: Mixed-reality simulation is an emerging tool for creating anatomical models for preoperative planning. Its use in neurosurgical training (NT) has been limited because of the difficulty in real-time interactive teaching. This study describes the development of a patient-specific, interactive mixed-reality NT system. The authors took cases of intracranial tumor resection or neurovascular compression (NVC) as examples to verify the technical feasibility and efficacy of the mixed-reality NT system for residents' training and preoperative planning. METHODS: This study prospectively enrolled 40 patients who suffered from trigeminal neuralgia, hemifacial spasms, or intracranial tumors. The authors used a series of software programs to process the multimodal imaging data, followed by uploading the holographic models online. They used a HoloLens or a standard iOS device to download and display the holographic models for training. Ten neurosurgical residents with different levels of surgical experience were trained with this mixed-reality NT system. Change in surgical strategy was recorded, and a questionnaire survey was conducted to evaluate the efficacy of the mixed-reality NT system. RESULTS: The system allows the trainer and trainee to view the mixed-reality model with either a HoloLens or an iPad/iPhone simultaneously online at different locations. Interactive manipulation and instant updates were able to be achieved during training. A clinical efficacy validation test was conducted. The surgeons changed their exploration strategy in 48.3% of the NVC cases. For residents with limited experience in surgery, the exploration strategy for 75.0% of all patients with NVC was changed after the residents were trained with the mixed-reality NT system. Of the 60 responses for intracranial tumors, the trainee changed the surgical posture in 19 (31.7%) cases. The change of the location (p = 0.0338) and size (p = 0.0056) of craniotomy are significantly related to the experience of the neurosurgeons. CONCLUSIONS: The mixed-reality NT system is available for local or real-time remote neurosurgical resident training. It may effectively help neurosurgeons in patient-specific training and planning of surgery for cases of NVC and intracranial tumor. The authors expect the system to have a broader application in neurosurgery in the near future.