HOXC10 has been reported to be upregulated in ovarian cancer (OC) tissues, attributing to the metastasis of OC. However, the specific functions of HOXC10 in OC, especially its role in chemoresistance, remain to be determined. Therefore, in this study, we explored the function and the underlying mechanisms of HOXC10 in carboplatin resistance of OC. A variety of approaches were utilized to analyze the expression of HOXC10 and its related genes. The effect of HOXC10 in cell growth and chemoresistance was investigated in carboplatin-resistant OC subline TOV21G-R and the parental TOV21G-P cells. ROC curve and survival analysis were conducted to determine the predictive value of HOXC10 and ABCC3 combination in carboplatin resistance and the prognosis of OC. Luciferase reporter assay and Chromatin immunoprecipitation (ChIP) assay were used to explore the direct regulation of β-catenin by HOXC10. Our results demonstrated that the expression of HOXC10 was upregulated both in the carboplatin-resistant OC tissues and TOV21G-R cells. Furthermore, the upregulation of HOXC10 could promote the expression of ABCC3 by transcriptionally upregulating β-catenin. Moreover, overexpression of HOXC10 could decrease the sensitivity of cells to carboplatin, while knocking down HOXC10 had the opposite effect both in vitro and in vivo . Therefore, the expression of HOXC10/ABCC3 could be a novel biomarker for predicting the carboplatin resistance and the prognosis of OC patients., Competing Interests: None., (AJCR Copyright © 2022.)