The average β values for p16, COAL1A2, DAPK, CCBE1, DCC, SALL3, NPY, TAC1, SST, GALR1, GALR2, NPY1R, NPY2R, NPY4R, NPY5R, TACR1, HCRTR1, HCRTR2, SSTR1, NPDDR1, NPFFR2, VEGFR1, VEGFR2, and VEGFR3 methylation were significantly higher in the HNSCC samples than in the normal samples (p < 0.05). The gene discussed is HCRTR1; the disease is head and neck squamous cell carcinoma.