Objective To investigate the effect of haloperitoxine melitraxine combined with paroxetine on somatic symptoms,sleep and cognitive function in patients with major depressive disorder（MDD）and its clinical application effects．Methods A retrospective analysis was performed on the relevant data of 120 patients with MDD who received treatment in our hospital from August 2020 to February 2023,and divided into conventional group（treated with paroxetine,55 cases）and combined group（haloperitoxetex melitraxine combined with paroxetine,65 cases）according to their different treatment regimens．The treatment duration of the two groups was 4 weeks,and the Hamilton Rating Scale for Depression（HAMD-17）score,Somatized Symptom Self-rating Scale（SSS）score,Sleep Quality Score（PSQI） and Neuropsychological State Rating Scale（RBANS）scores were compared before treatment and at the 2nd and 4th week of treatment．After treatment,the patients were followed up for 1 month,and the total efficacy and adverse reactions of the two groups of patients after treatment were compared．Results After 2 and 4 weeks of treatment,the combined group showed significantly higher RBANS scores compared to the control group（P<0.05）,while PSQI scores,SSS scores and HAMD-17 scores were significantly lower in the combined group compared to the control group（P<0.05）．One month after treatment,follow-up data showed that there was no statistically significant difference in the overall incidence of adverse reactions between the two groups（P>0.05）．Additionally,the total effective rate was significantly higher in the combined group compared to the control group（P<0.05）．Conclusions Haloperitoxine melitrexine combined with paroxetine has a definite clinical effect in patients with MDD,and can also help patients reduce somatization symptoms,improve patients' sleep quality,and improve patients' cognitive function．