Abstract: Objective Study the association of the Catechol-O-methyltransferase (COMT) gene single nucleotide polymorphism (SNP) Ala22/72Ser with schizophrenia (SCZ) in northern Han Chinese population. Methods In 506 SCZ patients, the genotype of Ala22/72Ser of COMT gene was determined by polymerase chain reaction (PCR) - sequencing; the severity of psychiatric symptoms of SCZ patients was scaled by positive and negative syndrome scale (PANSS); the expression of COMT gene was determined by Real-Time PCR. Results In SCZ patients, the overall score of positive scale and general psychopathology scale was significantly increased in Ser and Ser/Ala carriers (P < 0.01), and the expression of COMT gene in these patients was significantly decreased (P < 0.01). Conclusions The polymorphism of Ala22/72Ser in COMT gene was associated with the severity of positive symptoms and general psychopathology symptoms in SCZ patients, and associated with the expression of COMT gene.