The observation that HNSCC patients with low SOX2 and high SOX9 expression, identified here as a group with low DSS, highly expressed five key genes (INHBA, SERPINE1, THBS1, ITGB6 and LTBP1) of the TGF-β signaling pathway suggests a possible mechanistic explanation for the role of SOX2 and SOX9 in HNSCC patients’ survival. Here, SERPINE1 is linked to head and neck squamous cell carcinoma.