Head and neck squamous cell carcinoma (HNSCC) poses a significant global health challenge, with over 660,000 new cases diagnosed and more than 325,000 deaths each year. Despite advances in treatment, long-term survival rates for HNSCC patients remain disappointingly low, underscoring the critical need for innovative therapeutic strategies. This review delves into the role of super-enhancers in HNSCC, highlighting their pivotal function in regulating key oncogenes such as KLF4, FOSL1, and ΔNp63, which are crucial for tumor progression and metastasis. Moreover, it explores how super-enhancers contribute to the maintenance of cancer stem cell characteristics by controlling genes like SOX2, BRD4. thereby promoting self-renewal and pluripotency.The study also underscores the potential of BET bromodomain inhibitors, exemplified by JQ1, and CDK7 inhibitors like THZ1, which demonstrate substantial therapeutic promise by effectively disrupting the function of super-enhancers in HNSCC. Overall, this research provides a comprehensive overview of the importance of super-enhancers in HNSCC.