In the present study, Parkin was first identified to be upregulated after UBE2C was knocked down and functioned as the E3 ubiquitin ligase responsible for the K63‐linked ubiquitination of TOP2A, which not only emphasized the tumor‐suppressive role of Parkin in breast cancer but also clarified the mechanism by which UBE2C affected breast cancer cell sensitivity to doxorubicin. Here, TOP2A is linked to neoplasm.