Multiple myeloma (MM) is the second most common hematological malignancy. It is characterized by abnormal transformation and uncontrolled clonal proliferation of malignant plasma cells in the bone marrow (BM), which can destroy bone structure and inhibit hematopoiesis. Although there are new therapeutic methods, they are not curative, mainly because it is difficult to deliver an effective amount of drug to BM, leading to a failure to eradicate the MM cells inside the BM. BM homing is an important and unique characteristic of MM cells and it is mainly affected by surface molecules on the tumor cell membrane. Inspired by this mechanism, we developed an MM-mimicking nanocarrier by coating the bortezomib (BTZ)-loaded PCEC nanoparticles with the MM membrane. The MM-mimicking nanoparticles can enter the BM based on BM homing as a "Trojan Horse" and target the tumor cells through homologous targeting. In this way, drug availability at the myeloma site was enhanced so as to inhibit MM growth. In addition, these MM-mimicking nanoparticles could escape phagocytosis by the MPS and have a long circulation effect. The in vivo therapeutic results demonstrated an excellent treatment efficacy for MM. Accordingly, this strategy may be a promising platform for the treatment of MM. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.