In recent years, aurora kinase C (AURKC) has emerged as a potential therapeutic target for cancer, having been found to induce proliferation in a variety of cancers. However, at present, its precise mechanism remains unclear. In this study, the specific role of AURKC in renal clear cell carcinoma and its mechanism was investigated. The protein expression levels of AURKC were evaluated in clear cell carcinoma and adjacent normal tissues, followed by prognostic analysis. Subsequently, cell models with knocked-down and overexpressed AURKC were constructed for in vitro cell experiments, and tumor-bearing mouse models were constructed to confirm the specific role of AURKC in vivo. AURKC was found to be highly expressed in ccRCC, which was associated with poor prognosis. In the in vitro experiments, the expression levels of CyclinD1 and proliferating cell nuclear antigen (PCNA) proteins were downregulated after AURKC knockdown, and the cell proliferation ability was found to decrease significantly. After AURKC overexpression, the levels of ERp57 protein expression increased significantly, also significantly enhancing the cell proliferation ability. In addition, AURKC was found to interact with ERp57 and exhibited a colocalization relationship. In the in vivo experiments, AURKC downregulation significantly inhibited the expression of ERp57 protein and blocked the growth of tumor tissue in tumor-bearing mice. These results suggest that the abnormal expression of AURKC in ccRCC enhances the expression of ERp57 protein, thereby promoting the proliferation of clear cell renal cell carcinoma. Thus, AURKC shows potential as a target for the treatment of ccRCC.© The author(s).