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Insidious onset of ovarian cancer, most advanced-stage patients with ovarian cancer relapse and become refractory to conventional chemotherapy，seriously threatening the lives and health of female. Therefore, a critical restrictor to cure ovarian cancer is the development of chemoresistance. Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the EGF family of growth factors, has been proven to be a promising chemotherapeutic target for ovarian cancer. Cross-reacting material 197 (CRM197), a non-toxic mutant of diphtheria toxin, which could inhibit the chemoresistance of ovarian cancer through binding and inhibiting to HB-EGF specifically. Studies have indicated that CRM197 has a significant role in the treatment of multiple tumors and the chemoresistance of ovarian cancer, but the specific mechanisms remain to be further studied in drug-resistant ovarian cancer. The feather of CRM197 will be reviewed. We will also discuss the application of CRM197 in tumor therapy and the research progress that the combination of paclitaxel and cisplatin with CRM197 in paclitaxel- and cisplatin-resistant ovarian cancer. [ABSTRACT FROM AUTHOR]