Objective:Kidney cancer is a group of cancers occurred in the kidney. Hypoxia is a condition characterized by insuffi-cient oxygen supply in the body or specific organs. It has been proven to play an essential role in the pathogenesis and development of various cancer. However, the roles and mechanisms of hypoxia in kidney cancer have not been investigated clearly. In this study, we comprehensively analyzed the roles of hypoxia in kidney cancer. Methods:The RNA-Seq data of kidney cancer were downloaded from TCGA dataset. The survival of patients with differentially expressed hypoxia-related genes was analyzed with the survival package. The prognostic value of hypoxia-related genes was evaluated with univariate Cox regression analysis. The correlation of hypoxia-related genes to immune cells infiltration and gene mutation in kidney cancer was assessed. We identified 7 hypoxia-related genes of kidney cancer, with which we developed a hypoxia-related genes-based prognostic index using multivariate Cox regression analysis to establish the prog-nostic model. Results:The high-risk group showed lower survival compared with the low-risk group. HRGPI was an independent pre-dictor of kidney cancer, and it was associated with malignant stages. Hypoxia-related genes were correlated to activation of inflammatory pathways, infiltration of inflammatory cells, and expression of inhibitory immune checkpoints, indicating that hypoxia was related to im-mune response in kidney cancer. Lastly, we found that hypoxia was related to missense mutation in kidney cancer. Conclusion:Hy-poxia is a risk factor of kidney cancer. It can be regarded as the prognostic indicator and therapeutic target for the treatment of kidney cancer in the future.