This study investigates the role of cellular retinoic acid binding protein 2 (CRABP2) in chemotherapy resistance in ovarian cancer. CRABP2 is found to be upregulated in drug-resistant ovarian cancer tissues and cell lines, and its expression levels are closely related to tumor clinical stage and patient prognosis. CRABP2 is associated with high metabolic activity in drug-resistant cells, and all-trans retinoic acid (ATRA) exacerbates this activity. Mechanistically, CRABP2 upregulates the expression and nuclear localization of hypoxia-inducible factor 1α (HIF1α). Knocking down HIF1α in drug-resistant ovarian cancer cells blocks the resistance caused by CRABP2 to chemotherapy drugs. The study provides evidence that CRABP2 affects chemotherapy resistance by regulating HIF1α, suggesting a potential molecular mechanism for drug resistance and a possible molecular target for clinical treatment of ovarian cancer.This study investigates the role of cellular retinoic acid binding protein 2 (CRABP2) in chemotherapy resistance in ovarian cancer. CRABP2 is found to be upregulated in drug-resistant ovarian cancer tissues and cell lines, and its expression levels are closely related to tumor clinical stage and patient prognosis. CRABP2 is associated with high metabolic activity in drug-resistant cells, and all-trans retinoic acid (ATRA) exacerbates this activity. Mechanistically, CRABP2 upregulates the expression and nuclear localization of hypoxia-inducible factor 1α (HIF1α). Knocking down HIF1α in drug-resistant ovarian cancer cells blocks the resistance caused by CRABP2 to chemotherapy drugs. The study provides evidence that CRABP2 affects chemotherapy resistance by regulating HIF1α, suggesting a potential molecular mechanism for drug resistance and a possible molecular target for clinical treatment of ovarian cancer.