Doxorubicin (Dox) is a widely used chemotherapy drug to inhibit the growth and survival of human breast cancer (BC) cells. Presently, there is a pressing need for the development of new therapeutic strategies to enhance Dox efficacy by overcoming the resistance exhibited by breast cancer cells. Cadherin EGF LAG seven-pass G-type receptor 1 (CELSR1), belonging to the Flamingo subfamily, has been implicated in the progression of various tumors. However, the specific role and mechanisms of CELSR1 in the resistance of breast cancer to drug treatments have yet to be fully understood. This study aims to clarify the role of CELSR1 in conferring resistance to doxorubicin in breast cancer. Our findings demonstrate that CELSR1 expression is elevated in breast cancer tissues. Silencing of CELSR1 significantly reduced the proliferation and motility of breast cancer cells. Moreover, the ablation of CELSR1 decreased the resistance of breast cancer cells to doxorubicin treatment. At the molecular level, CELSR1 was found to activate the Wnt/Planar Cell Polarity (WNT/PCP) signaling pathway in breast cancer cells. In conclusion, CELSR1 plays a crucial role in promoting the migration of breast cancer cells and in enhancing their resistance to doxorubicin through the activation of the WNT/PCP pathway.