Abstract ： Objective ： To observe the clinical effect of qi- regulating and depression- resolving acupuncture method combined with western medicine on treatment- resistant depression (TRD) and its effect on brain function. Methods： A total of 40 TRD patients were divided into the trial group and the control group according to the random number table method， with 20 cases in each group. The control group was given routine western medicine for treatment，and the trial group was additionally treated with qi- regulating and depression- resolving acupuncture method based on the treatment of the control group. The scores of Hamilton Depression Scale- 24 (HAMD24) were compared before and after treatment between the two groups and of Visual Analogue Scale (VAS) were compared before and after treatment in the trial group； the clinical effects and differential results of resting- state functional magnetic resonance imaging (rs- fMRI) scanning were compared before and after treatment between the two group. The differential amplitude of low- frequency fluctuation (ALFF) values of brain regions and differential values of scores of HAMD24 and VAS were extracted for Pearson correlation analysis. Results：After treatment，the rate of response in the trial group was higher than that in the control group (P＜0.05). After treatment，the HAMS24 scores in the two groups were lower than those before treatment (P＜0.05)，and the VAS scores in the trial group was higher than that before treatment (P＜0.05)， and the HAMD- 24 scores in the trial group were lower than those in the control group (P＜0.05). After treatment， the main activated brain regions in the trial group included left cerebellar peduncle， left middle temporal gyrus， right middle temporal gyrus， and left caudate nucleus and the deactivated brain regions included peripheral cortex of right fissure calcarina， right caudate nucleus and right thalamus； the main activated brain regions in the control group include left middle temporal gyrus，left inferior temporal gyrus，superior frontal gyrus of right pars orbitalis and left middle frontal gyrus，and the deactivated brain regions included right cerebellum，left precuneus and right middle frontal gyrus. The ALFF value of time series of left caudate nucleus and left middle temporal gyrus were positively correlated with the differential value of HAMD24 in the trial group (r= 0.619， P＜0.05； r=0.662， P＜0.05)； the ALFF value of left caudate nucleus was negatively correlated with the differential value of VAS scores (r=- 0.513， P＜0.05)； the differential value of HAMD24 scores was negatively correlated with that of VAS scores (r=- 0.567， P＜0.05). No correlation was found in the control group. Conclusion： The therapy of qi- regulating and depression- resolving acupuncture method combined with western medicine has a definite curative effect on TRD，which can activate the ALFF signal strength of left caudate nucleus of patients， increase the threshold of pain perception， correct the abnormal perception and emotion control process， enhance the connection with other brain regions and effectively relieve the symptoms of depression.