Background <p>Systemic lupus erythematosus (SLE) is an incurable autoimmune disease that affects body tissues, but it can be managed with medication. Although therapeutic strategies for SLE have advanced, the underlying molecular mechanisms driving disease pathogenesis remain incompletely understood.</p> Methods <p>This study analyzed gene expression data from three GEO microarray datasets to explore immunity-related differentially expressed genes (DEGs) in SLE. Using WGCNA, we identified gene modules and integrated them with immune-related DEGs to find candidate hub genes, which were validated using RT-qPCR. We constructed a PPI network and performed gene enrichment analysis to identify nine hub genes through ROC curve analysis. We confirmed the link between these hub genes and immune cells, conducted GSEA, and predicted drugs, miRNAs, and transcription factors (TFs) targeting these genes. LASSO and ROC analyses validated a model using immunity-related DEGs.</p> Results <p>The forty immune-related DEGs were identified from a total of 1590 DEGs, 452 WGCN module genes, and 1791 immune genes. Nine hub genes (<i>MX1</i>, <i>OAS1</i>, <i>OASL</i>, <i>IRF7</i>, <i>RSAD2</i>, <i>EIF2AK2</i>, <i>ISG15</i>, <i>IFIH1</i>, and <i>STAT1</i>) were highlighted using Cytoscape and ROC analysis, with an AUC greater than 0.7. RT-qPCR confirmed significant overexpression of all hub genes except <i>STAT1</i> in SLE. ssGSEA and GSEA linked these genes to immune cell infiltration and pathways, including "cell cycle" and "RIG-I-like receptor signaling." A diagnostic model with three immune-related hub genes (<i>MX1</i>, <i>IRF7</i>, and <i>EIF2AK2</i>) demonstrated high accuracy (AUC &gt; 0.8) in distinguishing SLE from healthy controls. Additionally, 9 target drugs, 14 target miRNAs, and 23 TFs were identified for these hub genes.</p> Conclusions <p>MX1, IRF7, and EIF2AK2 may serve as candidate biomarkers for SLE and warrant further investigation.</p>