Renal clear cell carcinoma (RCCC) is the most common type of renal cancer, which is known for its high metastasis, aggressive behavior, and morphologic diversity. For early diagnosis and precise treatment, more biomarkers and therapeutic targets are badly needed. Centromere protein F (CENPF) is a microtubule-binding protein as well as a cell cycle-associated nuclear antigen. Recent studies demonstrated that CENPF affected multiple cellular processes, such as mitosis and vesicular transport. The wide effects of CENPF on the progression and metastasis of tumors have also been revealed, however, the effects of CENPF on renal cancer, especially RCCC, remain unknown. Herein, the obvious high expression of CENPF in human RCCC tissues was found, and the expression of CENPF was correlated with the prognosis and clinical pathological features including tumor size and tumor stage of RCCC patients. CENPF promoted the proliferation, migration, and invasion of RCCC cells in vitro, and contributed to tumor growth and metastasis in mice. Therefore, the involvement of CENPF in RCCC progression was confirmed and CENPF could act as a promising therapeutic target for RCCC treatment.