The present study aimed todevelop a prognostic model for HNSCC treatment on the basis of angiogenesis-related signatures. Head and Neck Squamous Cell Carcinoma (HNSCC) is the most frequent malignancy with poor prognostic outcomes in the head and neck. Angiogenesis plays a critical role in tumorigenesis and is expected to be an effective therapeutic target. The RNA-seq dataset TCGA-HNSCC and the hallmark gene set were used for angiogenesis-related RiskScore model construction. The RNA-seq data was downloaded from The Cancer Genome Atlas (TCGA), and the hallmark gene set was used to measure the angiogenesis score using the GSVA R package. Then, the optimal cutoff point for prognostic classification was calculated by the survminer package, and Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify angiogenesis gene modules . Multi/univariable and Lasso Cox analyses were performed to develop the RiskScore model, and the classifier efficiency was evaluated by the Receiver Operating Characteristic curve (ROC). Furthermore, a nomogram was designed for survival probability prediction, and the immune infiltration and immunotherapy differences among different risk patients were assessed. After calculating the angiogenesis score, we found that this indicator and patients' prognosis were closely correlated, especially when patients with a high angiogenesis score had a poor prognosis. Then, WGCNA identified a blue gene module positively correlated with angiogenesis. Multivariate and Lasso Cox analysis further identified 9 risk model genes for developing a RiskScore, which was used to divide low- and high- -risk groups of patients. Those with a high risk tended to show poor prognosis, immune infiltration, and higher immune escape. Finally, a nomogram was developed to optimize the risk model, and it exhibited excellent short- and long-term survival prediction performance. We constructed a reliable RiskScore model for the prognostic prediction of HNSCC patients, contributing to precise therapeutic intervention of the cancer.