CRABP2 affects chemotherapy resistance in ovarian cancer by regulating HIF1α expression. Ovarian cancer is a highly aggressive malignancy with poor prognosis, and chemotherapy resistance is a major challenge in treatment. This study reveals that CRABP2 is highly expressed in drug-resistant ovarian cancer tissues and is closely related to tumor progression and patient prognosis. CRABP2 is involved in the high metabolic activity of drug-resistant cells, and all-trans retinoic acid exacerbates this activity. Mechanistically, CRABP2 up-regulates HIF1α expression and increases its nuclear localization. Knocking down HIF1α in drug-resistant ovarian cancer cells blocks chemotherapy resistance. These findings suggest that CRABP2 affects chemotherapy resistance in ovarian cancer by regulating HIF1α expression. The study provides a possible molecular mechanism for drug resistance and a potential molecular target for clinical treatment of ovarian cancer. CRABP2 is associated with the prognosis of ovarian cancer patients and is highly expressed in ovarian cancer tissues, correlating with tumor malignancy, histopathological grade, clinical stage, and metastasis. CRABP2 may play a crucial role in the development, progression, and chemotherapy resistance of ovarian cancer. Further research on the molecular mechanisms involving CRABP2 could provide insights into potential therapeutic targets for ovarian cancer patients. The study shows that CRABP2 regulates the sensitivity of tumor cells to chemotherapy by influencing the metabolic activity of ovarian cancer cells. CRABP2 affects the expression and subcellular localization of HIF1α, and the effect of CRABP2 on drug sensitivity of ovarian cancer is dependent on HIF1α. HIF1α is highly expressed in drug-resistant cells and knocking down CRABP2 leads to decreased HIF1α expression. ATRA treatment increases HIF1α expression, suggesting a regulatory role of CRABP2 in HIF1α expression. Knocking down HIF1α enhances the sensitivity of cells to cisplatin, while overexpression of CRABP2 combined with HIF1α inhibitor treatment also increases cisplatin sensitivity. These findings highlight the dependence of CRABP2-mediated resistance on HIF1α expression and suggest that targeting HIF1α may overcome chemotherapy resistance in ovarian cancer. The study provides evidence that CRABP2 is closely related to the malignancy and drug resistance of ovarian cancer. CRABP2 affects the sensitivity of ovarian cancer cells to chemotherapy drugs by increasing the overall metabolic level in these cells, and by regulating the expression of HIF1α. Our findings suggest that targeting CRABP2 and HIF1α may be a promising strategy for overcoming chemotherapy resistance in ovarian cancer.CRABP2 affects chemotherapy resistance in ovarian cancer by regulating HIF1α expression. Ovarian cancer is a highly aggressive malignancy with poor prognosis, and chemotherapy resistance is a major challenge in treatment. This study reveals that CRABP2 is highly expressed in drug-resistant ovarian cancer tissues and is closely related to tumor progression and patient prognosis. CRABP2 is involved in the high metabolic activity of drug-resistant cells, and all-trans retinoic acid exacerbates this activity. Mechanistically, CRABP2 up-regulates HIF1α expression and increases its nuclear localization. Knocking down HIF1α in drug-resistant ovarian cancer cells blocks chemotherapy resistance. These findings suggest that CRABP2 affects chemotherapy resistance in ovarian cancer by regulating HIF1α expression. The study provides a possible molecular mechanism for drug resistance and a potential molecular target for clinical treatment of ovarian cancer. CRABP2 is associated with the prognosis of ovarian cancer patients and is highly expressed in ovarian cancer tissues, correlating with tumor malignancy, histopathological grade, clinical stage, and metastasis. CRABP2 may play a crucial role in the development, progression, and chemotherapy resistance of ovarian cancer. Further research on the molecular mechanisms involving CRABP2 could provide insights into potential therapeutic targets for ovarian cancer patients. The study shows that CRABP2 regulates the sensitivity of tumor cells to chemotherapy by influencing the metabolic activity of ovarian cancer cells. CRABP2 affects the expression and subcellular localization of HIF1α, and the effect of CRABP2 on drug sensitivity of ovarian cancer is dependent on HIF1α. HIF1α is highly expressed in drug-resistant cells and knocking down CRABP2 leads to decreased HIF1α expression. ATRA treatment increases HIF1α expression, suggesting a regulatory role of CRABP2 in HIF1α expression. Knocking down HIF1α enhances the sensitivity of cells to cisplatin, while overexpression of CRABP2 combined with HIF1α inhibitor treatment also increases cisplatin sensitivity. These findings highlight the dependence of CRABP2-mediated resistance on HIF1α expression and suggest that targeting HIF1α may overcome chemotherapy resistance in ovarian cancer. The study provides evidence that CRABP2 is closely related to the malignancy and drug resistance of ovarian cancer. CRABP2 affects the sensitivity of ovarian cancer cells to chemotherapy drugs by increasing the overall metabolic level in these cells, and by regulating the expression of HIF1α. Our findings suggest that targeting CRABP2 and HIF1α may be a promising strategy for overcoming chemotherapy resistance in ovarian cancer.