Breast cancer is one of the most common cancers among women in the United States. Although there are effective drugs, such as cisplatin, for treating advanced cancers, many patients eventually develop resistance. MicroRNAs (miRNAs) have emerged to play important roles in tumorigenesis and drug resistance. In this study, the authors observed a significant upregulation of miR-203 expression in human breast cancer tissues as compared to patient-matched nontumor breast tissues. Knockdown of miR-203 following cisplatin treatment enhances p53, p21, and Bax protein expression. Furthermore, knockdown of miR-203 sensitized human breast cancer MCF-7 cells to cisplatin-mediated apoptotic cell death, as evident from caspase-9 and caspase-7 activation, and poly(ADP-ribose) polymerase (PARP) cleavage. Moreover, the authors have demonstrated that suppressor of cytokine signaling 3 (SOCS3) is a novel target of miR-203, and cisplatin treatment in miR-203 knockdown MCF-7 cells enhanced SOCS3 expression. Exogenous expression of SOCS3 in MCF-7 cells increased sensitization to cisplatin-mediated apoptosis. Together, the results suggested a novel role of miR-203 in conferring cisplatin resistance through suppression of SOCS3, implicating an additional therapeutic strategy may be helpful to overcome cisplatin resistance for breast cancer patients.