Objective: Despite the standard treatment of head and neck squamous cell carcinoma (HNSCC) with chemotherapy, radiotherapy, and/or surgery, survival rates are still low. In recent years, a greater understanding of cellular interaction within the tumor microenvironment has allowed for the identification of (1) immune evasion that promotes the development and progression of tumors and (2) the application of immunotherapy. The aim of this study is to summarize the main findings of the research on the expression of immune- checkpoint inhibition molecules in HNSCC cases and possible immunotherapeutic use. Study Design: A narrative review of several relevant known papers (MEDLINE). Results: Studies have shown that 50% to 60% of HNSCC cases expressed high levels of PD-L1 in situ compared to peripheral blood. This high expression is associated with the high incidence of lymph node metastases, poor prognosis, and low survival. Experimental studies of immunotherapy with monoclonal antibodies against immune-checkpoint inhibition molecules showed a significant decrease in tumor growth, few adverse effects, and increased patient survival compared to conventional treatment. Conclusion: Adequate intervention against immune-checkpoint inhibition molecules shows positive treatment potential. However, it is necessary to standardize protocols for identifying these molecules within the tumor microenvironment for the selection of patients who may benefit from this immunotherapy. Objective: Despite the standard treatment of head and neck squamous cell carcinoma (HNSCC) with chemotherapy, radiotherapy, and/or surgery, survival rates are still low. In recent years, a greater understanding of cellular interaction within the tumor microenvironment has allowed for the identification of (1) immune evasion that promotes the development and progression of tumors and (2) the application of immunotherapy. The aim of this study is to summarize the main findings of the research on the expression of immune- checkpoint inhibition molecules in HNSCC cases and possible immunotherapeutic use. Study Design: A narrative review of several relevant known papers (MEDLINE). Results: Studies have shown that 50% to 60% of HNSCC cases expressed high levels of PD-L1 in situ compared to peripheral blood. This high expression is associated with the high incidence of lymph node metastases, poor prognosis, and low survival. Experimental studies of immunotherapy with monoclonal antibodies against immune-checkpoint inhibition molecules showed a significant decrease in tumor growth, few adverse effects, and increased patient survival compared to conventional treatment. Conclusion: Adequate intervention against immune-checkpoint inhibition molecules shows positive treatment potential. However, it is necessary to standardize protocols for identifying these molecules within the tumor microenvironment for the selection of patients who may benefit from this immunotherapy.