MicroRNA(miRNA) plays a role in the progresses of early embryogenesis and proliferation, differentiation, survival, apoptosis, metabolism, and energy balance of cell. MiRNA21 promotes adipogenic differentiation of mesenchymal stem cell(MSC) and inhibits the proliferation of human adipose-derived stem cell by transforming the growth factor(TGF)β-Smad pathway. Bone morphogenetic protein(BMP) receptor(BMPR)2 is a target of miRNA21, which is necessary for BMP9-induced osteogenesis. This finding indicates that miRNA21 is related to the osteogenic differentiation of stem cell. During the differentiation of MSC, miRNA21 down regulates the expression of sprout(SPRY)1 and SPRY2 to mediate the activation and duration of extracellular signal-regulated kinase-mitogen-activated protein kinase pathway and improves the differentiation potential of MSC. The overexpression of miRNA21 can also enhance the survival of MSC under hypoxia or serum-free condition, but the down regulation of miRNA21 accelerates cell apoptosis. Thus, biological function and regulatory mechanism during the differentiation of miRNA21 stem cell can lay basis for the usage of stem cell in tissue engineering and the prevention and treatment of diseases.