Objective To investigate the relationship between catecholamine oxygen methyltransferase （COMT） gene polymorphism and psychosocial factors and depression with chronic pain. Methods From January 2018 to December 2019， a total of 292 patients were included in the outpatient and inpatient treatment of the clinical psychology and pain department of People's Hospital of Xinjiang Uygur Autonomous Region. Fasting venous blood was drawn from all the patients. Screen the COMT gene rs6269 and rs4633 for single nucleotide polymorphism （SNP） by TaqMan SNP genotyping and sequencing method. According to whether depression was accompanied by chronic pain was divided into study group （141 cases） and control group （151 cases）. The general information， COMT gene polymorphism， Social Support Rating Scale （SSRS）， Self-Identity Scale （SIS） and Simple Coping Style Questionnaire （SCSQ） scores of the two groups were compared. The Global Pain Assessment Scale （GPS） was used to assess the degree of pain in patients with chronic pain. Multivariate Logistic regression was used to analyze the related factors of depression patients with chronic pain. Pearson correlation was used to analyze the correlation between psychosocial factors and the degree of pain in patients with depression and chronic pain. Results There was significant difference in gender and education between the two groups （P＜ 0.05）. The positive coping scores in the study group's SIS， SSRS， and SCSQ scales were lower than those in the control group， and the negative coping scores were higher than those in the control group. The difference was statistically significant （P＜ 0.01）. The frequency of the A allele at locus rs6269 of the COMT gene in the study group was higher than that in the control group， and the difference was statistically significant （P ＜ 0.05）. Multivariate Logistics regression analysis showed higher SIS score （OR=0.822， 95%CI=0.749- 0.903）， higher SSRS scores （OR=0.775， 95%CI=0.704-0.855） and higher positive coping scores in SCSQ （OR=0.001， 95%CI= ＜ 0.001-0.011）were protective factors for depression with chronic pain （P ＜ 0.05）. Female （OR=16.557， 95%CI=2.364-115.936）， education level of elementary school and below （OR=43.380， 95%CI=4.297-437.978）， lower negative coping scores in SCSQ （OR=187.293， 95%CI=10.826-3 240.198） and higher frequency of the A allele at position rs6269 of the COMT gene （OR=2.442， 95%CI=1.235-4.828） were risk factors for depression with chronic pain （P ＜ 0.05）. Pearson correlation analysis showed that SIS scores， SSRS scores， and SCSQ positive coping scores were negatively correlated with GPS scores （r=-0.689，-0.677， -0.736； P ＜ 0.05）， and were positively correlated with the mean score of negative coping in SCSQ （r=0.811， P ＜ 0.05）. Conclusions The frequency of A allele at rs6269 of COMT gene is correlated with depression and chronic pain； meanwhile， there is a certain correlation between the psychosocial state and chronic pain symptoms in patients with depression.