MicroRNA (miRNA) is a vital regulator for gene expression in eukaryotes, as well as an important component in the regulatory mechanism of tumor drug resistance. miRNA can abnormally regulate target genes through membrane receptor-mediated drug efflux, alteration of drug targets, block of cell apoptotic pathways, and change in DNA repair ability, etc., thus involving in the regulatory mechanism of multi-drug resistance. Important research advances in the regulation of growth and differentiation of cancer stem cells and the induction of multi-drug resistance via triggering the protective autophage by miRNA have been achieved. This paper reviews recent research progresses of mechanisms for the regulation of tumor cell multi-drug resistance by miRNAs.