Malignant carcinoma is one of the most threatening diseases to our human being’s life and health. However, chemotherapy, as one of the principal modes of treatment, especially for metastatic cancers, has been blocked by drug resistance, which contributing to disease progression and leading to a high mortality rate. Thus, research on both mechanisms and resolutions to chemo resistance seems extremely indispensable and urgent. MicroRNAs (miRNAs), the recently emerging class of novel molecules, have been reported to have close correlation with cancer. They act as oncogene or tumor suppressor gene, and growing evidence indicates that the desregulation of miRNAs involves in drug resistance. Alteration of miRNA’s expression leads to obviously different responsiveness to anticancer drugs. It implicates that miRNA may be a promising therapeutic target for improvement of chemoresistance, and it is inevitable that the settlement of drug resistance will be a giant leap and milestone in treatment of malignance. So in this review, we’ll elaborate the potential and promising role miRNAs playing in clinical treatment and progress.