Osteosarcoma is a common malignant bone tumour in adolescents and old people, with highly invasive and metastatic features and poor prognosis. This study aimed to explore the role of miR-384 in osteosarcoma MG63 cells by targeting SLBP. Cell viability, migration and invasion, apoptosis, as well as apoptosis-related factors were evaluated by CCK-8 assay, Transwell assay, flow cytometer and Western blotting, respectively. Dual-luciferase reporter assay was used to determine the target of miR-384. SLBP level was analyzed using qRT-PCR and Western blotting. Important factors of MEK/ERK and PI3K/AKT signalling pathways were analyzed using Western blotting. We found that miR-384 was down-regulated in osteosarcoma tissue samples and cell lines (MG63, U2OS and OS732). miR-384 overexpression inhibited viability, migration and invasion, but promoted apoptosis of MG63 cells; whereas, miR-384 silence exhibited the contrary effects on MG63 cells. SLBP was a target of miR-384. Knockdown of SLBP reversed the promoting effect of miR-384 silence on cells, indicating that miR-384 silence promoted growth and metastasis of MG63 cells by up-regulating SLBP. In conclusion, knocking down miR-384 promoted the growth and metastasis of osteosarcoma MG63 cells by up-regulating SLBP. To conclude, miR-384-SLBP may be a potential therapeutic target for osteosarcoma therapy.