Centromere protein H (CENPH), one of the essential component of active kinetochore, plays an important role in carcinogenesis of many cancer types. However, its expression signature and prognostic significance of renal cell carcinoma (RCC) are unclear. In the present study, we concluded that the expression of CENPH was prominently upregulated in RCC specimens and three RCC cell lines (ACHN, 786-O and A704). Immunohistochemical analysis revealed that RCCs exhibited higher levels of CENPH expression than normal renal tissues in paraffin-embedded archival specimens. Further statistical analysis suggested the upregulation of CENPH was positively correlated with the Fuhrman grade (P = 0.001), distant metastasis (P = 0.024) and clinical stage (P = 0.014). In addition, the CENPH served as an independent predictor of overall survival of RCC patients in multivariate analysis (P = 0.018). Furthermore, our in vitro assays of RCC cell lines indicated that knockdown of CENPH reduced cell proliferation, inhibited cell growth, and increased cell apoptosis. In conclusion, our data suggest that CENPH is a novel molecule involved in RCC progression, which provides a potential biomarker and therapeutic target.