Object Disrupted-in-Schizophrenia 1 (DISCt) is a major risk for schizophrenia (SCZ).A recent genetic association study has demonstrated that the genetic interaction between DISC1 and SLC12A2 (as known as NKCC 1) may be associated with the risk for SCZ, but until now, the interaction associated with SCZ risk has never been identified in the Han Chinese population.To explore the roles of single nucleotide polymorphisms (SNPs) in DISC1 and SLC12A2 genes as well as the interaction between gene-gene in the development of SCZ, we conducted a case-control study of Han Chinese.Methods We recruited 1413 SCZ patients and 1120 healthy controls.Two SNPs (rs821616 and rs1000731) in DISC1 and four SNPs (rs10089, rs10067555, rs2568928 and rs17607500) in SLC12A2 were genotyped using the LDR-PCR method.Results We observed that the AA genotype carriers of DISC1 SNP rs821616 had a significantly increased risk for SCZ in comparison with noncarriers (Padj < 0.0001), and a significant interaction between rs821616 and rs1000731 in DISC1 gene may be associated with SCZ (P =0.0010) by MDR analysis.However,the interactions between SNPs in DISC1 and SNPs in SLC12A2 were not observed.Conclusions This work provides new insight into the association of genetic variants in the DISC 1 gene with susceptibility to SCZ in Han Chinese.