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). This evidence concerns the gene NPFFR2 and head and neck squamous cell carcinoma.