Multivariate analysis demonstrated that TGFB1, MMP9, PLAU, CTSG, CCR8, SEMA5B, GAST, OSM, IL12RB2, TNFRSF25, and TNFRSF4 were potential independent prognostic biomarkers for HNSCC. The gene discussed is PLAU; the disease is head and neck squamous cell carcinoma.