In summary, we evaluated the diagnostic and prognostic capacity of PLAU based on TCGA database in HNSCC and demonstrated that hypomethylation and downregulation of miR-23b-3p were strongly associated with overexpression of PLAU via s Ras/MAPK and Akt/mTOR signaling pathways. The gene discussed is PLAU; the disease is head and neck squamous cell carcinoma.