We previously reported that EGFR activated the IKK/NF-κB pathway through mTORC1 downstream of PI3K/Akt in both cisplatin-sensitive and cisplatin-resistant HNSCC cells.25 Here, we examine the role of IKK/NF-κB in the regulation of HNSCC cell sensitivity to EGFR inhibitors, including Gefitinib and Erlotinib, in multiple HNSCC cell lines in vitro and in vivo. Here, EGFR is linked to head and neck squamous cell carcinoma.