The present study examined the correlation between variants in the d-amino acid oxidase activator (DAOA) locus and clinical symptoms and response to antipsychotics in schizophrenia. Case-control analysis and the family-based association test (FBAT) were performed to investigate whether four single nucleotide polymorphisms (SNPs) at DAOA gene are associated with schizophrenia. The association between the DAOA risk haplotype and clinical symptoms were examined by the positive and negative syndrome scale (PANSS) and the brief psychiatric rating scale (BPRS). Our findings showed that the SNP rs947267 was significantly associated with schizophrenia in both case control and familial trio samples (A>C, chi(2)=8.36, p=0.004; Z=2.335, p=0.019), as well as with specific haplotypes, in particular those formed by the A allele of rs947267. In addition, the risk haplotype AAG was significantly correlated with negative, depression and cognitive impairment factors of PANSS, even with the BPRS change scores after 6-week treatment of atypical antipsychotic drugs (p<0.05). These results support the hypothesis that variations in DAOA may play a role in schizophrenia and clinical characteristics.