Introduction and Importance: Near-infrared photoimmunotherapy (NIR-PIT, AlluminoxTM) uses an antibody-photoabsorber conjugate and light excitation, requiring precise illumination. Mixed reality (MR) technology can enhance medical procedures through advanced visualization and planning. Case Presentation: An 86-year-old man with recurrent oropharyngeal cancer and right cervical metastasis received NIR-PIT. Three-dimensional models from CT and FDG-PET/CT images were used as holograms on a head-mounted display (HMD) for precise light targeting. Clinical Discussion: HMD-MR technology was utilized for preoperative simulation and guided ideal light direction during surgery. This improved the effectiveness of NIR-PIT. Conclusion: Three months post-treatment, no residual lesion was observed, demonstrating the utility of HMD-MR technology in optimizing NIR-PIT outcomes.