To identify single-nucleotide polymorphisms that contribute to the genetic susceptibility to schizophrenia, we examined the potential association between schizophrenia and 9 single nucleotide polymorphisms (rs1530351, rs4791230, rs2869577, rs8077696, rs8070231, rs2292592, rs9916525, rs1122079, and rs4790953) in the G-protein signaling 9 gene. The participants included 395 schizophrenia subjects and 400 healthy controls. The selected single nucleotide polymorphisms were genotyped using mass spectrometry techniques. The allelic or genotypic frequencies of the rs4791230 (promoter region) polymorphisms in subjects with schizophrenia were significantly different from those in healthy controls. The subjects with schizophrenia had a significantly higher frequency of the G allele (P = 0.030, odds ratio = 1.589, 95% confidence interval = 1.042-2.422) of rs4791230. Strong linkage disequilibrium was observed in 4 blocks (D' > 0.9). Significantly fewer T-A (rs1530351-rs4791230) haplotypes (P = 0.029) were found in subjects with schizophrenia. These findings suggest a role of G-protein signaling 9 polymorphisms in schizophrenia among Han Chinese and may be informative for future genetic or neurobiological studies on schizophrenia.