Purpose To identify thedifferentially expressed circRNAs, mRNAs, and miRNAs between Osteosarcoma (OS) and normal tissues and the miRNAswhich significantly associated with prognosis of OS by analyzing geneexpression data in Gene Expression Omnibus (GEO) database.Methods Data on circRNAs,mRNAs, and miRNAs with differential expression in OS, compared to normal tissue, were obtained from the GEO database. circRNAs-miRNA interactions were predicted by the StarBase database. Different online toolsTargetScan andStarBase were cooperatively utilized to predict the mRNAs targeted by miRNAs. The plugins of BiNGOandClueGOin Cytoscape were used to conduct the functional and pathway enrichment analyses.Data on mRNAs expression and clinical in OS were obtained from GEO. Results A total of 6circRNAs (hsa_circ_0000006, hsa_circ_0046264, hsa_circ_0078767, hsa_circ_0094088, hsa_circ_0096041and hsa_circ_0049271) and 504 mRNAs were found to be upregulatedand 124 miRNAs were down-regulatedinOS tissues compared to normal tissues, based on the GEO database. The circRNAs-related ceRNA network was found to be associated with OS carcinogenesis by biofunctional analysis. FSCN1, MMYO10, NUDT11, SDC4, and UBE2V2high expressionswere associated with poor prognosis, and proved to be risk factors in patients with OS, based on the GEO database.Conclusion ThecircRNA-miRNA-mRNA network may provide valuable information on the mechanisms of OS initiation and progression. FSCN1, MMYO10, NUDT11, SDC4, and UBE2V2 proved to be a new potential prognostic biomarker for OS.