BackgroundSchizophrenia (SCZ) has a global prevalence of 1% and increases the risk of mortality, reducing life expectancy. There is growing evidence that the risk of this disorder is higher in males than in females and it tends to develop in early adulthood. The Y chromosome is thought to be involved in biological processes other than sex determination and spermatogenesis. Studies have shown that loss of chromosome Y (LOY) in peripheral blood cells is associated with a variety of diseases (including cancer) and increased all-cause mortality. An analysis of the relationship between LOY and schizophrenia is warranted.MethodsA total of 442 Chinese males (271 patients with schizophrenia vs. 171 controls) were included in this study. The copy numbers of the Y and X chromosomes were detected by positive droplets targeting the amelogenin gene (AMEL) on the Y chromosome and X chromosome (AMELY and AMELX, respectively), using droplet digital PCR (ddPCR). The LOY percentage was defined as the difference between the concentration of AMELX and the concentration of AMELY divided by the concentration of AMELX, denoted as (X - Y)/X.ResultsIn the Han Chinese population, the LOY percentage was higher in the schizophrenia group than in the control group (p< 0.05), although there was no significant difference in the presence of LOY between the two groups. A strong correlation was found between the average of the disease duration and the average of the LOY percentage (R2= 0.506,p= 0.032). The logistic regression analysis implied that the risk of LOY increases by 0.058 and 0.057 per year according to age at onset and duration of disease, respectively (ponset= 0.013,pduration= 0.017).ConclusionsIn the Han Chinese population, the LOY percentage of the disease group was significantly different from that of the control group. The age of onset and duration of schizophrenia might be risk factors for LOY in peripheral blood cells. A larger sample size and expanded clinical information are needed for more in-depth and specific analyses.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12888-023-04929-z.