Objective: This study aimed to use bioinformatics analysis to identify differentially expressed genes (DEGs) involved in the pathogenesis of schizophrenia and validate their mRNA expression levels through real-time quantitative PCR (qPCR). Material/methods: Datasets from the publicly available Gene Expression Omnibus (GEO) database were analyzed using R software to identify DEGs. Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, were conducted. A protein-protein interaction (PPI) network was constructed using Cytoscape software to identify key genes with notable expression changes. The expression levels of these key genes were subsequently validated in schizophrenia patients using qPCR to assess potential susceptibility genes. Results: In total, 813 DEGs were identified, with six key genes highlighted through GO analysis and PPI network screening. Among these, HDAC1, UBA52, and FYN demonstrated statistically significant differences in mRNA expression between schizophrenia patients and healthy controls (P < 0.05). Conclusions: This study identified several DEGs potentially linked to the pathogenesis of schizophrenia, suggesting that HDAC1, UBA52, and FYN could serve as candidate susceptibility genes and diagnostic biomarkers. These findings provide new insights and directions for future schizophrenia research.