In the present research, we discovered that HNSCC with a low-risk score exhibited significantly upmodulated expression of immune checkpoint genes including CD8A, HAVCR2, LAG3, IFNG (IFNγ), GZMB, CTLA4, TNF, CD274, PRF1, GZMA, and PDCD1. PDCD1 (PD1), CD274 (PD-L1), and CTLA4 are three already known immune checkpoints, numerous studies have achieved great success in immunotherapy targeting PD1/PDL1 therapy in different solid tumors in the past decade60, and other immune checkpoint inhibitors have also made substantial progress. Here, PRF1 is linked to head and neck squamous cell carcinoma.