MicroRNA (miR) plays an important role in tumorigenesis including malignant peripheral nerve sheath tumor (MPNST). miR-210 downregulation is frequently observed in a variety of tumors. In this study, miR-210 was identified as downregulated in MPNST cells, and its potential target ephrin-A3 (EFNA3) was upregulated in them compared with neurofibroma cells using quantitative real-time (qRT)-PCR. Luciferase reporter assay further demonstrates that EFNA3 is a target of miR-210. Then it is confirmed that miR-210 can regulate EFNA3 mRNA and protein expression in MPNST ST88-14 (NF1 wild-type) and sNF96.2 (NF1 mutant type) cell lines. The functions of miR-210 in MPNST cells were investigated, and the results showed that overexpression of miR-210 increased cellular viability, colony formation, S phase percentage, and invasiveness of MPNST cells. Inversely, inhibition of miR-210 expression induced suppression of proliferation and invasion of MPNST cells. These results suggest that miR-210-mediated EFNA3 promotion of proliferation and invasion of MPNST cells plays an important role in MPNST tumorigenesis and progression. miR-210 and EFNA3 may be candidate novel therapeutic targets for MPNST.