Schizophrenia (SCZ) is a severe psychiatric disorder associated with many different risk factors, both genetic and environmental. A recent genome-wide association study (GWAS) of Han Chinese identified three single-nucleotide polymorphisms (SNPs rs11038167, rs11038172, and rs835784) in the tetraspanins gene TSPAN18 as possible susceptibility loci for schizophrenia. Hoping to validate these findings, we conducted a case-control study of Han Chinese with 1093 schizophrenia cases and 1022 healthy controls. Using the LDR-PCR method to genotype polymorphisms in TSPAN18, we found no significant differences (P>0.05) between patients and controls in either the allele or genotype frequency of the SNPs rs11038167 and rs11038172. We did find, however, that the frequency of the ‘A’ allele of SNP rs835784 is significantly higher in patients than in controls. We further observed a significant association (OR  = 1.197, 95%CI  = 1.047–1.369) between risk for SCZ and this ‘A’ allele. These results confirm the significant association, in Han Chinese populations, of increased SCZ risk and the variant of the TSPAN18 gene containing the ‘A’ allele of SNP rs835784.