BACKGROUND Amounting evidence indicate that miRNAs play an important role in the development of various cancers. MiR-495 is a potential tumor suppressor in cancers, however its role in melanoma is still elusive. The study aimed to investigate the role of miR-495 and the underlying mechanisms in melanoma cells. METHODS The levels of miR-495 in melanoma tissues and cell lines were measured by quantitative real-time polymerase chain reaction. Mimics of miR-495 was transfected into human melanoma cells A375 and MeWo. Cell viability of miR-495-transfected cells was assayed by MTT assay. Cell migration and invasion of miR-495 transfected cells were measured by wound healing assay and transwell assay, respectively. Nucleosome enzyme-linked immunosorbent assay was performed to measure the apoptosis induced by overexpression of miR-495. Luciferase reporter assays were performed to verify the interaction between miR-495 and its target PBX3. RESULTS It was found that the expression levels of miR-495 were down-regulated in melanoma tissues and cells. Moreover, overexpression of miR-495 inhibited melanoma cell proliferation, migration and invasion in vitro. PBX3 was identified as a target for inhibition by miR-495 and was confirmed by luciferase assay, quantitative real-time polymerase chain reaction and western blot. We also indicated that silencing of PBX3 also repressed melanoma cell proliferation, migration and invasion in vitro. CONCLUSIONS In summary, our findings demonstrated that miR-495 functions as a tumor suppressor in human melanoma via directly targeting PBX3.