MicroRNAs (miRNAs) play essential roles in the progression of osteosarcoma.Interestingly, though, the expression level of miR-377 is lower in 7 osteosarcoma samples than in normal human osteoblasts; the role of miR-377 in osteosarcoma is unclear.Consistent with this, we observed that miR-377 is expressed at a lower level in osteosarcoma cell line MG-63 than in human fetal osteoblastic cell line hFOB 1.19.Moreover, miR-377 overexpression remarkably reduced cell proliferation and suppressed invasion of MG-63 cells but had no effect on MG-63 cell apoptosis.Because cyclin-dependent kinase 6 (CDK6) could be a potential target of miR-377 in osteosarcoma cells, we overexpressed CDK6 and found that this attenuated the tumor suppressive effects of miR-377 on cell proliferation.Our data suggest that miR-377can suppress proliferation of human osteosarcoma MG-63 cells in part by targeting CDK6.