Objective To explore the correlation between 5-HTTLPR and rs25531(A>G) in the promoter region of 5-hydroxytryptamine transporter gene (SLC6A4) and schizophrenia in Chinese Han population. Methods 624 patients with schizophrenia and 683 healthy controls were genotyped with polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) technique. Results The genotypes of 5-HTTLPR included short (S), long (L), and extra-long (XL) alleles. The difference in distribution of 5-HTTLPR genotypes between the case group and the control group was statistically significant. S/XL genotype was a risk factor of schizophrenia (P=0.042, OR=1.79, 95%CI1.01-3.17). The difference in distribution of 5-HTTLPR-rs25531 genotypes between the case group and the control group was statistically significant. S/XLA and LG/XLA genotypes were risk factors of schizophrenia (P=0.042, OR=1.79, 95%CI1.01-3.17; P=0.034, OR=3.69, 95%CI  1.01-13.48). Conclusion The polymorphism of 5-HTTLPR and rs25531(A>G) in the promoter region of SLC6A4 gene is associated with schizophrenia in Chinese Han population.