This study investigates the genetic association between methyl-CpG-binding domain (MBD) gene polymorphisms and schizophrenia. A total of 200 family trios consisting of fathers, mothers, and affected offspring with schizophrenia were recruited as our participants. Four tag SNPs on MBD1 (rs125555, rs140689, rs140687, and rs140686), three tag SNPs on MBD2 (rs3876254, rs7614, and rs1145317), and three tag SNPs on MBD3 (rs7252741, rs4807934, and rs4807122) genes were tested using the PCR-based ligase detection reaction (PCR-LDR). The transmission disequilibrium test showed that rs1145317 on the MBD2 gene was significantly overtransmitted from parents to schizophrenic offspring (P=0.026). The haplotype-based haplotype relative risk test revealed that the haplotype rs7614–rs1145317 (A–G) was associated with schizophrenia (P=0.029). Our finding suggests that the MBD2 gene may be a susceptibility gene for schizophrenia.