BACKGROUND: Schizophrenia (SZ), a chronic and widespread brain disorder, presents with complex etiology and pathogenesis that remain inadequately understood. Despite the absence of a universally recognized endophenotype, peripheral blood mononuclear cells (PBMCs) serve as a robust model for investigating intracellular alterations linked to SZ. AIM: To preliminarily investigate potential pathogenic mechanisms and identify novel biomarkers for SZ. METHODS: PBMCs from SZ patients were subjected to integrative transcriptomic and proteomic analyses to uncover differentially expressed genes (DEGs) and differentially expressed proteins while mapping putative disease-associated signaling pathways. Key findings were validated using western blot (WB) and real-time fluorescence quantitative PCR (RT-qPCR). RNAi-lentivirus was employed to transfect rat hippocampal CA1 neurons in vitro, with subsequent verification of target gene expression RESULTS: The integration of transcriptomic and proteomic analyses identified 6079 co-expressed genes, among which 25 DEGs were significantly altered between the SZ group and healthy controls. Notably, haptoglobin (