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Eliminating stem cell\u2010like cancer cells is an extremely promising but challenging strategy for treating ICC. A recently developed synthetic retinoid, sulfarotene, abrogates proliferation, and induces apoptosis of tumor\u2010repopulating cells (TRCs) that exhibit stem cell\u2010like properties, yet its effect and underlying mechanisms remain elusive in ICC. It is found that although 5\u2010fluorouracil, cisplatin, pemigatinib, and gemcitabine all inhibit ICC\u2010TRCs, sulfarotene demonstrates superior efficacy. Sulfarotene induces retinoic acid receptor alpha (RAR\u0251) translocation from the cytoplasm to the nucleus, suppressing P\u2010selectin expression at the transcriptional level. Moreover, it directly interacts with fucosyltransferase 8 (FUT8), inhibiting the core fucosylation of P\u2010selectin glycoprotein ligand 1 (PSGL1). These actions collectively inhibit ICC\u2010TRCs via destroying PSGL1\u2010regulated cytoskeleton. 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