Osteosarcoma is one of the most common types of bone sarcoma with a poor prognosis. However, identifying the predictive factors that contribute to the response to neoadjuvant chemotherapy remains a significant challenge.A public data series (GSE87437) was downloaded to identify differentially expressed genes (DEGs) and differentially expressed lncRNAs (DElncRNAs) between osteosarcoma patients that do and do not respond to preoperative chemotherapy. Subsequently, functional analysis of the transcriptome expression profile, regulatory networks of DEGs and DElncRNAs, competing endogenous RNAs (ceRNA) and protein-protein interaction networks were performed. Furthermore, the function, pathway, and survival analysis of hub genes was performed and drug and disease relationship prediction of DElncRNA was carried out.A total of 626 DEGs, 26 DElncRNAs, and 18 hub genes were identified. However, only one gene and two lncRNAs were found to be suitable as candidate gene and lncRNAs respectively.The DEGs, hub genes, candidate gene, and candidate lncRNAs screened out in this context were considered as potential biomarkers for the response to neoadjuvant chemotherapy of osteosarcoma.© 2021. Huazhong University of Science and Technology.