More than 80% of HNSCCs exhibit overexpression of EGFR in the membrane, and hyperactivity EGFR plays an important role in tumorigenesis development and drug-resistance mechanisms by activating various signaling pathways, including the PI3K/AKT, RAS/MEK/ERK, and Janus kinase (JAK)/STAT pathways, in HNSCC. The gene discussed is EGFR; the disease is head and neck squamous cell carcinoma.