In this study, variants of two genes coding for cytochrome P450 enzyme (CYP3A4 and CYP3A5) were analysed in a case-control sample using 398 schizophrenic patients and 391 healthy controls. All subjects were unrelated Han Chinese from Shanghai. No difference was observed on the allelic or genotypic distribution of CYP3A4 and CYP3A5 gene polymorphisms between the groups. However, the two-marker haplotypes covering components CYP3A41G and CYP3A53 were observed to be significantly associated with schizophrenia (corrected global p=0.0009). In addition, we identified one common risk haplotype, G/G (present in 59.5% of the general population). The results suggest that CYP3A4 and CYP3A5 might play a role in genetic susceptibility to schizophrenia. However, confirmatory studies in independent samples are needed.