The ubiquitin-proteasome system (UPS) with a capacity of degrading multiple intracellular proteins is an essential regulator in tumor immunosurveillance. Tumor cells that escape from recognition and destruction of immune system have been consistently characterized an important hallmark in the setting of tumor progression. Little know about the exact functions of UPS-related genes (UPSGs) and their relationships with antitumor immunity in head and neck squamous cell carcinoma (HNSCC) patients. In this study, for the first time, we comprehensively identified 114 differentially expressed UPSGs (DEUPSGs) and constructed a prognostic risk model based on the eight DEUPSGs (BRCA1, OSTM1, PCGF2, PSMD2, SOCS1, UCHL1, UHRF1, and USP54) in the TCGA-HNSCC database. This risk model was validated using multiple data sets (all P < 0.05). The high-risk score was found to be an independently prognostic factor in HNSCC patients and was significantly correlated with T cells suppression. Accordingly, our risk model can act as a prognostic signature and provide a novel concept for improving the precise immunotherapy for patients with HNSCC.