In conclusion, we performed a comprehensive bioinformatics study of HNSCC and constructed 12 ion channel gene signatures (ANO1, AQP1, AQP5, AQP9, BEST2, CHRNA5, KCNJ15, KCNG1, SCNN1G, SCN4A, TRPC1, and VDAC1). The gene discussed is AQP5; the disease is head and neck squamous cell carcinoma.