Furthermore,the up-regulated expression of ZFAS1 was closely related to poor prognosis. In vitro, loss-of-function experiments showed that ZFAS1 knockdown significantly suppressed the proliferation, induced cycle arrest at G0/G1 phase and enhance apoptosis. In vivo, ZFAS1 knockdown inhibited the tumor growth. Bioinformatics online programs predicted that ZFAS1 sponge miR-486 at 3'-UTR with complementary binding sites, which was validated using luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Rescue experiments confirmed that miR-486 could reverse the functions of ZFAS1 on osteosarcoma genesis. In conclusion, our results demonstrate that ZFAS1 act as competing endogenous RNA (ceRNA) for miR- 486, and act as oncogene in osteosarcoma tumorigenesis, and discover the functional regulatory pathway of ZFAS1 sponging miR-486.