Based on LASSO Cox regression model, nine pyroptosis-related genes (TTLL1, TRIML2, DYNC1I1, KLHL35, CAMK2N1, TNFRSF18, GLDC, SPINK5, and DKK1) were used to construct a pyroptosis-related gene signature, which had good ability to predict the prognosis of HNSCC. The gene discussed is KLHL35; the disease is head and neck squamous cell carcinoma.