Head and neck squamous cell carcinomas (HNSCCs) are the seventh most common malignancy worldwide. HNSCCs are highly heterogeneous diseases with varied genetic aberrations, biological behaviors, response to treatments and clinical outcomes, which arise from different anatomical subsites. Meanwhile, HPV-associated HNSCCs represent a distinct entity, and their prevalence has increased substantially in the recent decades. Indeed, about 60% of patients have advanced diseases at diagnosis and the prognosis of HNSCCs remains poor. Immunotherapy has significantly improved the clinical outcome and patient survival in various stages of HNSCCs and is still under active investigation. In this chapter, the epidemiology, etiology, and genetics of HNSCCs are reviewed. The conventional treatment approaches for HNSCCs are described and the rationale of immunotherapy for HNSCCs is introduced. Then, recent advances in immunotherapy for HNSCCs from treatment-refractory to treatment-naive setting for recurrent or metastatic diseases, from definitive treatment to neoadjuvant and adjuvant treatment setting for locally advanced diseases, with a particular focus on the progress of immune checkpoint inhibitors (ICIs), are summarized. Finally, potential biomarkers of immunotherapy in HNSCCs are discussed, and it is expected to facilitate future studies.