Therefore, based on PRGs in these three subtypes, we selected nine genes (TTLL1, TRIML2, DYNC1I1, KLHL35, CAMK2N1, TNFRSF18, GLDC, SPINK5, and DKK1) related to HNSCC prognosis and conducted a new prognostic feature for HNSCC using LASSO regression algorithm program and univariate Cox regression analysis. This evidence concerns the gene TTLL1 and head and neck squamous cell carcinoma.