These data indicate that targeting TRPM7 sensitizes HNSCC to cisplatin; altered TRPM7 expression, independent of or within the context of calcium signaling pathway induction, is involved in HNSCC cell proliferation, invasion, migration, evasion of cell death signaling, remodeling of the extracellular matrix, EMT, and chemoresistance. This evidence concerns the gene TRPM7 and head and neck squamous cell carcinoma.