In conclusion, we estimated the level of infiltrating stromal and immune cells in the TME of HNSCC patients and constructed a ceRNA network, in which FOXP3, IL10RA, STAT5A, PRF1, IL2RA, miR-148a-3p, miR-3065-3p, CXCR2P1, HNRNPA1P21, CTA-384D8.36, and IGHV1OR15-2 were significantly correlated with the OS of HNSCC patients. Here, PRF1 is linked to head and neck squamous cell carcinoma.