The key findings of the data presented here center around the induction of an IL-1α/IL-1R/MyD88-dependent signaling pathway due to cetuximab treatment in HNSCC cells, and that IL-1α may be a promising immunotherapeutic strategy alone and in combination with cetuximab for the treatment of HNSCC. Here, IL1R1 is linked to head and neck squamous cell carcinoma.