AbstractBackgroundmultidrug resistance (MDR) is One of the foremost challenges in overcoming breast cancer. Various molecular processes are involved in the development of MDR in breast cancer cells, including over expression of ABC transporters such asABCG2(BCRP), increase breast cancer stem cells drug resistance, and epithelial mesenchymal transition.AimsIn the present study, we used bioinformatics and experimental analysis to investigate the role of miR‐548 K, in the modulating ofABCG2,in MDR breast cancer cells.Methods and ResultsIn silico inspections introduce 14 microRNAs targeting 3′‐UTR region of ABCG2 transcripts, which are probably involved in breast cancer drug resistance. An association was highlighted between miR‐548 k with ABC transporter family. The expression level ofABCG2gene in MCF7‐MX cell lines was significantly more than MCF7 cell lines. On the other hand, we increased the expression of miR‐548 K in MCF7‐MX and MCF7 cell lines through its transfection, which dramatically coincided with decreasion in theABCG2transcripts level. Additional studies on patient samples revealed that the expression ofABCG2showed an increase inABCG2level in neoadjuvant chemotherapy drugs resistance (NCDR) patients compared to primary pre‐operative chemotherapy drugs response (PCDR) patients. Also, a reduction in the expression of miR‐548 K in NCDR patients was revealed.ConclusionThe results of our study suggest that miR‐548 K may be involved in modulating the expression ofABCG2in MDR breast cancer cells.