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Recently, the advent of immune checkpoint blockade, particularly agents targeting programmed death-1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4, has introduced significant advancements within the oncological landscape, including for HNSCC. The introduction of immune checkpoint inhibitors, specifically the PD-1 blockers pembrolizumab and nivolumab, has established a new therapeutic standard for recurrent\/metastatic HNSCC (R\/M HNSCC). However, the clinical benefit is not universal, as a primary challenge remains the high incidence of treatment resistance. Consequently, a majority of patients (approximately 60%-70%) with R\/M HNSCC derive minimal or no benefit from this form of immunotherapy, highlighting the critical need to understand the underlying resistance mechanisms. This review comprehensively discusses the types of immunotherapy resistance in HNSCC and the underlying mechanisms contributing to resistance. 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