Abstract: Head and neck squamous cell carcinoma (HNSCC) is a highly invasive malignant tumor. Although patients receive standard treatment, the risk of local recurrence and distant metastasis remains high, resulting in a poor prognosis. In recent years, immune checkpoint inhibitors (ICIs) have shown significant efficacy in the treatment of a variety of solid tumors and have changed the treatment modality for many advanced tumors. However, in some patients, immunotherapy not only failed to bring survival benefits but also led to the rapid growth of tumor lesions in a short period of time, which is clinically known as hyperprogressive disease (HPD). There is limited research on the mechanism, clinical predictors, and coping strategies for immunotherapy-related hyperprogression. Therefore, this article focuses on HNSCC and reviews the current research on HPD to provide a scientific basis for optimizing immunotherapy.