Serotonin transmission has long been suspected as being involved in the pathogenesis of schizophrenia. 5-HTT is a promising candidate gene for schizophrenia due to its critical role in regulating serotonin transmission and role in the mechanism of the atypical antipsychotic drugs. A common polymorphism STin2 VNTR in the 5-HTT gene has been extensively investigated in the genetic association studies, but the results are conflicting. Meanwhile, the SNPs of the 5-HTT gene have been much less explored. We therefore conducted a case-control study of the association between STin2 VNTR and three tagging SNPs in 5-HTT and schizophrenia in the Han Chinese population based on a cohort of 329 schizophrenic patients and 288 control subjects. No association was found in the single locus, but haplotype-based analyses revealed significant association between two haplotypes with schizophrenia even after Bonferroni correction (P=0.00000538 and 0.011).