In the present study, a series of bioinformatic analysis identified 10 hub genes (IRF7, IFI35, IFIT3, ISG15, OAS1, MX2, OASL, IFI6, IFITM1, and IFIH1) between SLE and HC samples based on the gene expression profiles obtained from the GSE49454 and GSE20864 datasets. This evidence concerns the gene ISG15 and systemic lupus erythematosus.