Abstract Drug resistance in epithelial ovarian cancer is reportedly attributed to the existence of cancer stem cells, because in most cancers, CSCs still remain after chemotherapy. To overcome this limitation, novel therapeutic strategies are required to prevent cancer recurrence and chemotherapy-resistant cancers by targeting cancer stem cells. We screened an FDA-approved compound and clinical libraries, and found several small molecule drugs that target ovarian CSCs. These drugs decreased sphere formation, viability, and proliferation, and induced apoptosis in ovarian CSCs. Since these drugs harbor target proteins, we investigated the expression of the target proteins in ovarian CSC and found the increased level of the protein expression and new therapeutic markers of ovarian CSCs. Downregulation of these genes reduced the stem-cell-like properties of ovarianCSCs. Expressions of these three genes are negatively correlated with the survival rate of patient groups. In combination therapy with chemo agents, synergistic ect was shown in inhibiting the viability and proliferation of ovarian CSCs. Our results suggested that these may be potential therapeutic drugs for preventing ovarian cancer recurrence. Citation Format: Dong Kyu Choi, Sang Hyun Min. Screening of novel therapeutic markers for ovarian cancer stem cells [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr A021.