Schizophrenia's heritability and familial transmission have been known for several decades. The male-specific Y chromosome plays an important role in schizophrenia. Short tandem repeats (STRs)have been recognized as risk genes in the development of schizophrenia. Here, we investigated the association between male schizophrenia and Y-chromosomal STRs loci.We recruited 355 patients with schizophrenia and 473 healthy males for physical examination and amplified them with a PowerPlex 21 System fluorescence-labeled composite amplification System. Then, the resultant products were separated by electrophoresis and further detected. Finally, differences in allele and genotype frequency distributions of STR loci were observed.Our results showed that all 20 STR loci were in accordance with Hardy-Weinberg's law (p > .05). There were statistically significant differences in alleles of D13S317 and D5S818 loci and genotype frequency distribution between the two groups (alleles: p = .039, p = .022, respectively; genotype: p = .0004, p = .011, respectively). However, there was no difference in the other autosomal 18 STR loci between the two groups (p > .05). Univariate analysis showed that the frequency distribution differences of allele 11 and genotype 10-11 at the D13S317 locus between the two groups were significant (compared to the controls, p = 0.005, odds ratio (OR) = 1.37, 95%b confidence interval (CI) = 1.10-1.71, compared to the controls, p = .0000002, OR = 3.92, 95% CI = 2.27-6.77, respectively). The frequency distribution differences of allele 7 and genotype 7-10 at D5S818 between the two groups were significant (compared to the controls, p = .0006, OR = 3.42, 95% CI = 1.63-7.16, compared to the controls, p = .0011, OR = 8.24, 95% CI = 1.83-37.05, respectively).Polymorphisms of the D13S317 and D5S818 loci may be predisposing factors for schizophrenia.© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.