BACKGROUND: This study investigates the role of the KEAP1-NRF2/HO-1 signaling pathway in inducing ferroptosis and contributing to neuronal damage in schizophrenia. METHODS: We retrieved schizophrenia-related data and ferroptosis-related genes from the RNA microarray dataset GSE27383 and FerrDB database, respectively. Bioinformatics data identified KEAP1 as a downregulated gene, which was validated using qRT-PCR and Western blot. We assessed intracellular Fe RESULTS: Patients with schizophrenia exhibited underexpression of KEAP1, a key regulator of ferroptosis, along with elevated intracellular Fe CONCLUSION: Our findings indicate that the KEAP1-NRF2/HO-1 pathway contributes to ferroptosis and neuronal injury in schizophrenia.