As a potential drug/gene delivery system, the ultrasound-targeted microbubble destruction (UtMD) system can be used as a vehicle as well as increasing the permeability of biological barriers to enhance the effect of tumor treatment. However, the effect of UTMD in the tumor EMT process is unknown. In this study, we aimed to investigate the potential and mechanism of UtMD induced oxidative stress in inhibiting EMT of breast cancer. Human breast MDA231 cells were treated with microbubble (MB), ultrasound (US) and UTMD, respectively. The generation of oxidative stress, the levels of miR-200c, ZEB1 and vimentin, and the numbers of migratory cells were evaluated quantitatively and qualitatively by the measurement of intracellular reactive oxygen species (ROS), qRT-PCR, western blot assay, and transwell assay. Then, to evaluate the role of UTMD-induced oxidative stress and miR-200c in the epithelial-mesenchymal transition (eMt) inhibition, the RoS scavenger n-acetyl-L-cysteine (nAc) and miR-200c inhibitor were used before UTMD treatment. We found that UTMD induced oxidative stress, upregulated the expression of miR-200c, downregulated the expression of ZEB1 and vimentin and suppressed the MDA231 cell migration. The addition of NAC and miR-200c inhibitor had an opposite impact on the expression of miR-200c and ZEB1, thus hindered the effects of UTMD on MDA231 cells EMT. In conclusion, UTMD can inhibit the EMT characteristics of MDA231 cells. The mechanism may be related to the regulation of the miR-200c/ZEB1 axis through the generation of ROS induced by UTMD, which may provide a new strategy to prevent the tumor cells EMT under UTMD treatment. The metastasis of cancer is a complicated process, and is the main cause of the patients' death. Epithelial-mesenchymal transition (EMT) is a key regulator of aggressive invasion and metastasis in tumorigenesis 1,2. During the EMT process, the epithelial cells lose the apical-basal polarity and cell-cell adhesion and get mesenchymal characteristics 3. The major EMT markers comprise epithelial markers, such as E-cadherin, and mesenchymal markers, such as vimentin, N-cadherin, and fibronectin. Zinc finger E-box binding homeobox transcription factor 1 (ZEB1) is a critical EMT-related transcription factor (EMT-TF). ZEB1 knockdown represses vimentin expression, upregulated E-cadherin expression, and inhibited cell proliferation and metastasis 4. Another central regulator of EMT is the microRNA-200 (miR-200) family, which consists of 5 members (miR-200a,-200b,-200c,-141 and-429) 5. Mounting evidence suggests that ZEB1 and miR-200c reciprocally control their expression through a negative regulatory loop, and miR-200c repression or ZEB1 expression has been associated with a worse prognosis in several carcinomas, such as breast and ovarian cancer 5-7. Ultrasound (US) imaging is a real-time imaging technique which allows visualization of organ structure. Microbubbles (MBs) are used as ultrasonic contrast agents which increase the image contrast due to the acoustic mismatch between the gas an...