Background: Clear cell renal cell carcinoma (ccRCC) is considered the most common histopathological subtype and constituting nearly 70% of all primary renal cell carcinomas. Dysregulation of proteins related to Renin-Angiotensin System (RAS) could offer a new prognostic indicator in this malignant neoplasm. Objective: This study aimed to demonstrate renin (REN) & erythropoietin (EPO) immunohistochemical expression in ccRCC cases & their expression was correlated with the clinicopathological data & survival of the studied cases to explore their potential prognostic role. Material and methods: This retrospective research carried upon 30 cases ccRCC immunohistochemically stained with REN and EPO & the results to be correlated with different clinicopathological variables and patient's survival. Results: REN & EPO were expressed in 70% & 80% of ccRCC cases, respectively. Positive REN expression was significantly related to younger patients' age, lower nuclear grade, absence of (renal vein thrombosis, necrosis, perirenal fat invasion, renal sinus invasion, lymph/vascular invasion, lymph node metastasis & distant metastasis) and lower American Joint Committee on Cancer (AJCC) stage. While EPO positive expression was significantly related to younger patients' age, greater grade, greater T stage & higher AJCC stage. Negative REN & positive EPO expression were correlated to poor 5-year overall survival (P= 0.008 & 0.045 respectively) & disease-free survival (P= 0.006 & 0.038 respectively). Conclusion: Renin and Erythropoietin expression may be prognostic indicators of ccRCC and could predict patient's survival. Further researches are recommended to declare prognostic significance of other proteins of RAS pathway providing new insights and treatment modalities of ccRCC.