Previous studies showed that EGR3 gene located in chromosome 8p21.3 was involved in the etiology of schizophrenia. However, the finding failed to be replicated in several case-control studies. To investigate the genetic role of the EGR3 gene in Chinese psychiatric patients, we genotyped five single nucleotide polymorphisms (SNPs) in EGR3 gene locus using 93 nuclear families in Han Chinese, and performed transmission disequilibrium test (TDT). In this study, two SNPs (rs1996147 and rs3750192) showed significant association with schizophrenia (c2>4.40, P<0.05). In the linkage disequilibrium analysis, the significant association was also found in two- (rs3750192-rs35201266), three- (rs1877670- rs3750192-rs7009708) and four-SNP (rs1996147-rs1877670-rs3750192-rs7009708) tests of haplotype analyses (c2>7.10, global P<0.05). Overall, the results suggested that EGR3 gene may play an important role in schizophrenia susceptibility in the Han Chinese population, and further functional exploration of the EGR3 gene will contribute to the underlying molecular mechanism for schizophrenia pathogenesis.