Neuroblastoma, featured by a high rate of spontaneous remissions, is the most common extra-cranial solid tumor in infants and children. Numerous reports have demonstrated that MicroRNAs (miRNAs) play essential roles in cancer progression, including cell proliferation, apoptosis, invasion, metastasis and angiogenesis. miR-421 functions as an onco-miR in some malignancies. However, its role in neuroblastoma remains poorly understood. In the present study, we found that miR-421 was increased in neuroblastoma tissues compared with matched adjacent normal tissues. Forced overexpression of miR-421 substantially enhanced cell proliferation, cell-cycle progression, migration, and invasion of neuroblastoma cells. At the molecular level, tumor suppressor menin was found to be a target of miR-421. Furthermore, downregulation of menin by small interfering RNA oligos exhibited similar effects with overexpression of miR-421. On the other hand, overexpression of menin partially reversed the proliferative effects of miR-421 in neuroblastoma cells. Collectively, miR-421 may promote neuroblastoma cell growth and motility partially by targeting menin.