Objective To explore the relationship between the rs1061325 polymorphism of clathrin heavy chain like 1 (CLTCL1) gene and schizophrenia in Chinese Han population. Methods A total of 662 schizophrenia patients in the inpatient department and outpatient department of Shanghai Mental Health Center of Shanghai Jiao Tong University School of Medicine from 2007 to 2008 were selected as the case group. At the same time, a total of 414 healthy volunteers were recruited as the control group. The rs1061325 polymorphism of the CLTCL1 gene was genotyped by TaqMan genotyping assay. the severity of psychiatric symptoms in the case group were assessed by the Positive and Negative Symptom Scale (PANSS), and the correlation between PANSS score and different genotypes was analyzed. Results There was no significant difference in the frequency distribution of rs1061325 alleles and genotype between the case group and the control group (χ2 =0.25, P=0.62; χ2 =0.28,P=0.87). There was no significant difference in genotype distribution under codominant, dominant, recessive, over-dominant and log-additive models (P>0.05). The rs1061325 genotype polymorphism in patients with schizophrenia had no significant effect on the age of onset[(24.15±6.71) years], the course of the disease [(31.23±9.49) years] and BMI [(26.46±5.28) kg/m2 ] (F=1.15, P=0.32; F=0.33, P=0.72; F=0.75, P=0.48)There was no correlation between rs1061325 genotype polymorphism and PANSS positive symptom score, negative symptom score, general psychopathology score and PANSS total score (F=1.26, P=0.29; F=0.37, P=0.69; F=0.34, P=0.72; F=0.49, P=0.62). Conclusions There was no association between rs1061325 polymorphism of CLTCL1 gene and schizophrenia in Chinese Han population.