In this study, we identified 12 prognostic genes (the NAD(P)H: quinone oxidoreductase 1 (NQO1), peroxiredoxin 6 (PRDX6), heat shock protein family A member 5 (HSPA5), voltage-dependent anion channel 2 (VDAC2), GABA type A receptor-associated protein-like protein 2 (GABARAPL2), ATP5MC3, autophagy-related gene 5 (ATG5), G6PD, AURKA, CDKN2A, mitogen-activated protein kinase (MAPK9), and Caveolin1 (CAV1)) associated with both cuproptosis and ferroptosis in HNSCC. Here, PRDX6 is linked to head and neck squamous cell carcinoma.