MicroRNAs　(miRNAs)　have　emerged　as　important　regulators　in　multiple　myeloma　(MM).　miR-1271　is　a　tumor　suppressor　in　many　cancer　types.　However,　the　biological　role　of　miR-1271　in　MM　remains　unclear.　In　the　present　study,　we　elucidated　the　biological　role　of　miR-1271　in　MM.　Results　showed　that　miR-1271　was　significantly　decreased　in　primary　MM　cells　from　MM　patients　and　MM　cell　lines.　Overexpression　of　miR-1271　inhibited　proliferation　and　promoted　apoptosis　of　MM　cells.　Conversely,　suppression　of　miR-1271　showed　the　opposite　effect.　Bioinformatics　algorithm　analysis　predicted　that　smoothened　(SMO),　the　activator　of　Hedgehog　(HH)　signaling　pathway,　was　a　direct　target　of　miR-1271　that　was　experimentally　verified　by　a　Dual-luciferase　reporter　assay.　Furthermore,　overexpression　of　miR-1271　inhibited　SMO　expression　and　HH　signaling　pathway.　Conversely,　the　restoration　of　SMO　expression　markedly　abolished　the　effect　of　miR-1271　overexpression　on　cell　proliferation,　apoptosis　and　HH　signaling　pathway　in　MM　cells.　Taken　together,　the　present　study　suggests　that　miR-1271　functions　as　a　tumor　suppressor　that　inhibits　proliferation　and　promotes　apoptosis　of　MM　cells　through　inhibiting　SMO-mediated　HH　signaling　pathway.　This　finding　implies　that　miR-1271　is　a　potential　therapeutic　target　for　the　treatment　of　MM.