Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and may progress to acute myeloid leukemia (AML). MicroRNAs (miRNA/miRs) as oncogenes or tumor suppressors regulate a number of biological processes including cell proliferation, cell cycle and apoptosis in different types of cancer cells. Recently, it has been reported that miR-21 as an oncogene is overexpressed and directly targets SMAD-7 in MDS. However, little is known about the mechanism of miR-21 in the progression of MDS. In the present study, the role of miR-21 in the proliferation and apoptosis of SKM-1 cells, an acute myeloid leukemia cell line established in the AML/MDS leukemic phase was investigated. The present results demonstrated that downregulation of miR-21 inhibited proliferation, induced apoptosis and caused G1 phase cell cycle arrest of SKM-1 cells. In addition, the expression levels of apoptosis regulator Bcl-2 (bcl2), cyclinD1 and phosphorylated-protein kinase B (AKT) were significantly decreased in SKM-1 cells transfected with the miR-21 inhibitor, whilst the expression levels of phosphatase and tensin homolog (PTEN), bcl-associated protein X (bax) and cleaved caspase 3 were significantly elevated. Furthermore, knockdown of Akt by small interfering (si)RNA significantly increased the expression of bax, cleaved caspase 3 and reduced the expression of bcl2 and cyclinD1 in SKM-1 cells. Taken together, these data indicate that miR-21 targets the PTEN/AKT pathway in the pathogenesis of MDS and could be a potential target for MDS therapy.