Background. Diabetic nephropathy (DN), a significant cause of chronic kidney disease (CKD), is a devastating disease worldwide. Objective. The aim of this study was to reveal crucial genes closely linked to the molecular mechanism of tubulointerstitial injury in DN. Methods. The Gene Expression Omnibus (GEO) database was used to download the datasets. Based on this, a weighted gene coexpression network analysis (WGCNA) network was constructed to detect DN-related modules and hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichments were performed on the selected hub genes and modules. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed on the obtained gene signature. Results. The WGCNA network was constructed based on 3019 genes, and nine gene coexpression modules were generated. A total of 57 genes, including 34 genes in the magenta module and 23 genes in the purple module, were adapted as hub genes. 61 significantly downregulated and 119 upregulated genes were screened as differentially expressed genes (DEGs). 25 overlapping genes between hub genes chosen from WGCNA and DEG were identified. Through LASSO analysis, a 9-gene signature may be a potential prognostic biomarker for DN. To further explore the potential mechanism of DN, the different immune cell infiltrations between tubulointerstitial samples of DN and healthy samples were estimated. Conclusions. This bioinformatics study identified CX3CR1, HRG, LTF, TUBA1A, GADD45B, PDK4, CLIC5, NDNF, and SOCS2 as candidate biomarkers for the diagnosis of DN. Moreover, DN tends to own a higher proportion of memory B cell.