Purpose: To explore the role of ORC6 in clear cell renal cell carcinoma (ccRCC). Methods: The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) database was used to investigate the association between ORC6 expression and clinicopathological parameters. Furthermore, the expression level of ORC6 was determined in human RCC tissues and cell lines by western blot and PCR. Receiver operating characteristics curves and Kaplan-Meier curves were performed to assess the diagnostic and prognostic value of ORC6 in RCC. Results: High expression of ORC6 predicted shorter overall survival (OS) (P<0.0001) and acted as an independent prognostic factor. ORC6 could distinguish the tumor from the normal patient (area under the curve=0.8827, P<0.0001). The expression of ORC6 was associated with the P53 signaling pathway, cell cycle, and DNA replication. Conclusion: ORC6 could serve as a useful diagnostic and prognostic biomarker and a potential therapeutic target for ccRCC.