The PIK3C3 gene has been implicated as a candidate gene for schizophrenia by functional evidence and genetic association studies. A series of previous studies have found susceptibility SNPs in promoter region. To further verify its susceptibility to schizophrenia in the Chinese population and the function of the polymorphisms, we performed a case control study in 556 unrelated schizophrenia patients and 563 normal controls as well as an in vitro functional analysis. In our association analysis of-432C-/T, we discovered obvious differences in allele frequency between patients and controls (P=0.017). A T/C haplotype constructed by -432C-/T and -86insC, which are tightly linked with each other (r(2)=1) can significantly weaken promoter's transcriptional activity by 20% (p=0.002 by t-test). Though we cannot exclude the possibility that susceptibility of -432C-/T is caused by its linkage disequilibrium with other causal variants, our results do support PIK3C3 play a significant role in the etiology of schizophrenia.