This review discusses the role of immune regulation in treating head and neck squamous cell carcinoma (HNSCC). HNSCC is a common malignancy with limited treatment options, and conventional therapies like surgery, radiation, and chemotherapy often have limited success and significant side effects. Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has emerged as a promising treatment modality. ICIs target proteins such as PD-1 and CTLA-4 to enhance the immune response against cancer cells. PD-1 inhibitors like nivolumab and pembrolizumab have shown promising results in advanced HNSCC patients. However, resistance and limited patient response remain challenges. The tumor microenvironment (TME) plays a critical role in immune evasion, with immunosuppressive cells like Tregs and MDSCs contributing to tumor progression. Other immune checkpoint proteins, including TIM-3, LAG-3, GITR, and VISTA, are also being explored for their potential in immunotherapy. Combination therapies, such as PD-1/CTLA-4 or PD-1/GITR, are being investigated to enhance antitumor effects. Additionally, immunotherapy is being combined with other treatments like radiotherapy and chemotherapy to improve outcomes. Despite progress, challenges such as immune resistance, tumor immune evasion, and adverse effects remain. Future research aims to identify predictive biomarkers and optimize treatment strategies for better patient outcomes.This review discusses the role of immune regulation in treating head and neck squamous cell carcinoma (HNSCC). HNSCC is a common malignancy with limited treatment options, and conventional therapies like surgery, radiation, and chemotherapy often have limited success and significant side effects. Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has emerged as a promising treatment modality. ICIs target proteins such as PD-1 and CTLA-4 to enhance the immune response against cancer cells. PD-1 inhibitors like nivolumab and pembrolizumab have shown promising results in advanced HNSCC patients. However, resistance and limited patient response remain challenges. The tumor microenvironment (TME) plays a critical role in immune evasion, with immunosuppressive cells like Tregs and MDSCs contributing to tumor progression. Other immune checkpoint proteins, including TIM-3, LAG-3, GITR, and VISTA, are also being explored for their potential in immunotherapy. Combination therapies, such as PD-1/CTLA-4 or PD-1/GITR, are being investigated to enhance antitumor effects. Additionally, immunotherapy is being combined with other treatments like radiotherapy and chemotherapy to improve outcomes. Despite progress, challenges such as immune resistance, tumor immune evasion, and adverse effects remain. Future research aims to identify predictive biomarkers and optimize treatment strategies for better patient outcomes.