In this study, we constructed a prognostic signature consisting of 9 circadian rhythm-related genes (ADA, ICOS, ALG3, STC1, CYP4X1, EZH2, OLR1, PLEKHA6, and STARD4) to predict the prognosis of HNSCC patients. This evidence concerns the gene EZH2 and head and neck squamous cell carcinoma.