Objective · To explore the association of zinc finger ZBTB22 gene single nucleotide polymorphisms (SNPs) and schizophrenia in Han Chinese population. Methods · A case-control study was designedgenotyping four SNPs (rs3130100, rs1061783, rs1061801 and rs3130099) in 658 schizophrenia patients and 658 healthy controls of Chinese Han origin. SHEsis was used to analyze genotypic and allelic distributions, linkage disequilibrium and haplotype distribution. Results · rs3130100, rs1061783, and rs3130099 showed significant differences between the cases and controls in allele frequencies (P<0.05 after Bonferroni correction), but no statistically significant differences were found in genotype frequencies after Bonferroni correction. Strong linkage disequilibrium was found among the four SNPs, and the frequency of haplotype TCGA significantly decreased in the schizophrenia patients (P0.015 after Bonferroni correction). Conclusion · The ZBTB22 SNPs rs3130100, rs1061783 and rs3130099 may be associated with schizophrenia in Han Chinese population.