Abstract:[Objective] The purpose of this study is to identify the potential long non-coding RNAs (lncRNAs) and signaling pathways involved in Steroid-induced Osteonecrosis of Femoral Head (SONFH), and to investigate their molecular mechanisms.[Methods]Microarray data (GSE123568) were downloaded from NCBI-GEO and analyzed using bioinformatics tools. By analyzing Differentially Expressed Genes (DEG), Kyoto Encyclopedia of Genes and Genomes (KEGG) amplification pathways, Gene Ontology (GO), and finally identified a protein-protein interaction (PPI) network and identified 3 key Noncoding genes and 1 key mRNA. We further studied the co-expression profiles of mRNAs, miRNAs and lncRNAs in steroid-induced necrosis of the femoral head, established a specific competitive endogenous RNA (ceRNA) network for steroid-induced femoral head necrosis, analyzed immune infiltration, and explored the relationship between DEG and immune cells. Correlation. Finally verified with GSE26316.[Results]A total of 3 lncRNAs (C20orf197 MIR22HG XIST), 21 miRNAs and 37 mRNAs, and a key axis lncRNA-miRNA-mRNA (XIST/Has-miR-217/FOXO3) that may play an important role in SONFH were obtained in this study. In addition, by analyzing its immune infiltration, it was found that SONFH tissues contained a higher proportion of CD4 naive T cells compared with normal tissues (P < 0.05), and finally the expression level of the key gene FOXO3 was verified from the GSE26316 dataset. [Conclusion]C20orf197, MIR22HG and XIST are potential markers in the pathogenesis of SONFH, and the gene axis XIST/Has-miR-217/FOXO3 plays an important role in the occurrence and development of SONFH.