Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy that is the sixth most common neoplasm in the world. Despite advances in treatments involving surgery, radiation, and chemotherapy, the 5-year survival has remained at less than 50% for the past 30 years, primarily because of local recurrences. Thus, the possibility of immunotherapeutic approaches for patients with HNSCC has gained interest. Unfortunately, patients with HNSCC have profound immune defects that are associated with increased recurrence. This review aims to provide an overview of both the defensive and immune subversive mechanisms by which patients with HNSCC can protect themselves from immune antitumor assault.