Herein, this article analyzes the expression characteristic and clinical significance of PD-1 and PD-L1 in HNSCC, focuses on how tumor cells and stromal cells expressing PD-1 and PD-L1 play immunosuppressive roles in HNSCC, and reviews the present development landscape of PD-1/PD-L1 inhibitors, which may be useful to HNSCC patients with recurrence and metastasis. Here, CD274 is linked to head and neck squamous cell carcinoma.