Background: The prognosis of cervical cancer (CC) is poor and not accurately reflected by the primary tumor node metastasis staging system. Our study aimed to develop a novel survival-prediction model. Methods: Hallmarks of CC were quantified using single-sample gene set enrichment analysis and univariate Cox proportional hazards analysis. We linked gene expression, hypoxia, and angiogenesis using weighted gene co-expression network analysis (WGCNA). Univariate and multivariate Cox regression was combined with the random forest algorithm to construct a prognostic model. We further evaluated the survival predictive power of the gene signature using Kaplan-Meier analysis and receiver operating characteristic (ROC) curves. Results: Hypoxia and angiogenesis were the leading risk factors contributing to poor overall survival (OS) of patients with CC. We identified 109 candidate genes using WGCNA and univariate Cox regression. Our established prognostic model contained six genes (MOCSI, PPP1R14A, ESM1, DES, ITGA5, and SERPINF1). Kaplan-Meier analysis indicated that high-risk patients had worse OS (hazard ratio = 4.63, p < 0.001). Our model had high predictive power according to the ROC curve. The C-index indicated that the risk score was a better predictor of survival than other clinicopathological variables. Additionally, univariate and multivariate Cox regressions indicated that the risk score was the only independent risk factor for poor OS. The risk score was also an independent predictor in the validation set (GSE52903). Bivariate survival prediction suggested that patients exhibited poor prognosis if they had high z-scores for hypoxia or angiogenesis and high risk scores. Conclusions: We established a six-gene survival prediction model associated with hypoxia and angiogenesis. This novel model accurately predicts survival and also provides potential therapeutic targets.Copyright © 2022 Liu, Zhu, Wang and Wu.