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Schizophrenia (SCZ) is a common mental disease causing severe chronic disability. Epigenetic changes in HPA axis-related genes are considered to play an important role in SCZ pathogenesis. Unfortunately, the methylation status of the corticotropin-releasing hormone ( CRH ) gene, which is the central driving force in the HPA axis, has not been reported in SCZ patients. Here, we used the sodium bisulfite and MethylTarget methods to detect the DNA methylation status of the CRH gene coding region in peripheral blood samples from 70 schizophrenic patients and 68 healthy controls. The results showed that the methylation level of the CRH gene CDS was significantly increased in SCZ patients, especially in the male subgroup. In conclusion, this study showed that differences in CRH gene CDS methylation were detectable in the peripheral blood of SCZ patients and that epigenetic abnormalities in the CRH gene were closely related to SCZ, revealing that epigenetic processes may mediate the pathophysiology of SCZ. Further research should address the underlying mechanism whereby CRH gene methylation regulates the occurrence and development of SCZ.