Head and Neck Squamous Cell Carcinoma (HNSCC) ranks as the sixth most common cancer globally, with a five-year survival rate still less than 50%. Recently, pyroptosis, a newly identified form of programmed cell death, has gained significant attention. This process is activated by inflammatory Caspases and relies on the gasdermin protein family to form pores in the cell membrane. Studies indicate that pyroptosis plays a vital role in both tumor progression and therapy resistance. Activated inflammasomes, as members of the Nucleotide-binding Oligomerization Domain-like Receptor (NLR) family, trigger Caspase-1, thereby inducing inflammatory effects and pyroptosis, further influencing the course of the tumor disease. However, research relating pyroptosis to HNSCC remains limited. This article reviews current findings and underscores the importance of further studies focusing on the role of pyroptosis in HNSCC.