Breast cancer (BC) is the most common cancer among women that is responsible for the most of the cancerrelated death in worldwide. Drug resistance is remaining as a significant clinical obstacle to treat BC patients effectively. Therefore, to help overcome this problem, it is necessary to understand the mechanisms of drug resistance. microRNAs classify as highly conserved non-coding RNAs (~22 nucleotides) and interact with mRNAs-coding genes for direct post-transcriptional repression. It has been reported that miR-21 is overexpressed and also acts as oncomiR in many human malignancies by targeting of several tumor suppressor genes–associated with apoptosis, proliferation and metastasis. Specifically, it has been reported that miR-21 is responsible for the drug resistance and its overexpression is related to the development of Multi Drug Resistance (MDR) in breast cancer. In this review, we discussed about the role of miR-21 on the drug resistance of breast cancer.