Ｏｂｊｅｃｔｉｖｅ　To explore the correlation between rs4680 polymorphic site of catechol-O-methyl transferase (COMT) gene and postoperative pain so as to provide theoretical evidence for individualized medicine.　Methods　A total of eighty-three patients ［aging 29-58, American Society of Anesthesiologists (ASA) Ⅰ or Ⅱ］ scheduled for mastectomy under general anesthesia was selected. Polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) was adopted to identify their genotype of rs4680 polymorphic site of COMT. The patients were divided as a wild-type group(Val/Val, VV, n=51), a hybrid subtype group (Val/Met, VM, n=23) and a mutation-type group(Met/Met, MM, n=9). Then the tertiary structures of COMT protein before and after mutation were predicted through homology modeling and the physicochemical property of the protein was analyzed. Preoperative anesthesia was conducted by intravenous-inhalation combined anesthesia and postoperative anesthesia by patient controlled intravenous analgesia (PCIA). The number of effective and ineffective compressions of the analgesic pump within 24 h was recorded. Patients′ pain was assessed 2, 4, 8 h and 24 h after operation by the Numerical Rating Scale (NRS) and then its correlation with different genotypes was analyzed.　Results　The mutation of rs4680 polymorphic site of COMT has no significant effects on tertiary structures of COMT protein but it affected the physicochemical property of COMT protein. MM patients showed remarkably more PCIA press time than VV and VM patients 24 h after surgery (P<0.05). MM patients presented markedly more PCIA effective press time than VV patients (P<0.05). There was no significant difference in NRS score between the three genotypes at each postoperative point.　Conclusions　Single polymorphic site rs4680 may have little influence on individual difference of postoperative pain for patient with breast cancer.