Objective To identify hub genes for major depressive disorder (MDD) by weighted gene co-expression network analysis (WGCNA) combined with differential expressions gene (DEG) analysis. Methods The mRNA microarray data of postmortem brain tissues from MDD patients and healthy volunteers were obtained from the Gene Expression Omnibus. Both WGCNA and DEG analysis were used to screen the modules most significantly associated with MDD and DEGs, Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed on the WGCNA module genes and DEGs, intersection genes were obtained by matching DEGs to WGCNA module genes, and receiver operating characteristic curves were plotted to assess the abilities of the intersection genes to diagnose MDD. Results At the end, 10 genes were obtained, including FLJ20021, FLJ30058, NNAT, MRPS12, KCNK4, TROVE2, MESP1, MIF, TMEM93, and SYNGR1; all of which had the potential to diagnose MDD effectively.Conclusion FLJ20021, FLJ30058, NNAT, MRPS12, KCNK4, TROVE2, MESP1, MIF, TMEM93, and SYNGR1 can be used as biomarkers to assist in the diagnosis of MDD.