Multivariate analysis demonstrated that TGFB1, MMP9, PLAU, CTSG, CCR8, SEMA5B, GAST, OSM, IL12RB2, TNFRSF25, and TNFRSF4 were potential independent prognostic biomarkers for HNSCC. Here, MMP9 is linked to head and neck squamous cell carcinoma.