Clear cell renal cell carcinoma (ccRCC) is a highly aggressive disease and ∼30% of the patients are diagnosed at the metastatic stage. Even with new targeted therapies, the average progression-free survival and overall survival (OS) rates are dismal. Thus, biomarkers for early detection and progression could improve disease outcome. The role of C1q/tumor necrosis factor (C1QTNF) family in cancer is an emerging field of research. However, the biological function of C1q/tumor necrosis factor-related protein 6 () and its prognostic value in cancer are rarely reported. This study aimed to evaluate as a potential diagnostic and prognostic biomarker for ccRCC. In this study, we enrolled 993 ccRCC samples (data from our cohort, The Cancer Genome Atlas, and Gene Expression Omnibus) with expression to explore its role and mechanism in ccRCC. The diagnostic power of was determined by receiver operating characteristic curve analysis and its prognostic value was evaluated by Kaplan-Meier analysis and Cox regression models, respectively. In addition, the gene set enrichment analysis was performed to unveil the molecular mechanism of in ccRCC. We demonstrated that was overexpressed in ccRCC, and elevated expression correlated with clinical progression. Besides, served as a new diagnostic biomarker for renal cell carcinoma. Moreover, is an independent risk factor for OS in ccRCC patients. Furthermore, -related signaling pathways activated in ccRCC are mainly enriched in cell cycle, epithelial-mesenchymal transition, and angiogenesis signaling pathways. Taken together, our results provided insights in understanding the potential role of in promoting tumor growth, invasion, and metastasis, and its use as a novel cancer diagnostic and prognostic biomarker for ccRCC.