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Background Depression belongs to the category of emotional disorders in traditional Chinese medicine, and its pathogenesis can be explained by the theory of "kidney brain harmony". Whether kidney tonifying and brain strengthening acupuncture therapy can be used to treat elderly depression has not been reported in the past. Objective Exploring the effect of tonifying the kidney and strengthening the brain acupuncture therapy based on the theory of "kidney brain coordination" combined with sertraline on improving the emotional and cognitive functions of elderly depression patients. Methods This trial has been registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2400081227). Eighty-six elderly patients with depression admitted to the Department of Mental Health and Psychology of the General Hospital of Northern Theater Command between March 2023 and March 2024 were selected as the research subjects, they were randomly divided into an observation group (n=43) and a control group (n=43). The patients in the control group were treated with sertraline alone, while the patients in the observation group were treated with kidney tonifying and brain strengthening acupuncture combined with sertraline. All patients were treated for 4 weeks. Before and after treatment, evaluate depressive mood using the 17 item Hamilton Depression Scale (HAMD-17), evaluate cognitive function using the Wisconsin Card Sorting Test, detect platelet count (PLT), mononuclear cell count (MONO), neutrophil count (NC), lymphocyte count (LC), and calculate systemic immune inflammation index (SII), systemic inflammatory response index (SIRI). Compare the HAMD-17 scores, cognitive function, SII and SIRI of the two groups before and after treatment. The relationship between the change values of HAMD-17 scores and cognitive function with SII and SIRI in the observation group was analyzed by Pearson correlation analysis, and the clinical efficacy of the two groups was compared. Results The HAMD-17 score in the observation group was lower than the control group after treatment (P<0.05). The percentage of correct responses and conceptualization level in the Wisconsin Card Sorting Test in the observation group after treatment was higher than that in the control group (P<0.05). The SII and SIRI of the observation group was lower than the control group after treatment (P<0.05). The changes in SII before and after treatment in the observation group were positively correlated with the changes in HAMD-17 score (r=0.536, P<0.05). The changes in SII were negatively correlated with the percentage of correct responses to the Wisconsin Card Sorting Test (r=-0.621, P<0.05) and the percentage of conceptualization level (r=-0.482, P<0.05), respectively. The change in SIRI score was positively correlated with the change in HAMD-17 score (r=0.429, P<0.05). The SIRI change values were negatively correlated with the percentage of correct responses to the Wisconsin Card Sorting Test (r=-0.378, P<0.05) and the percentage of conceptualization level (r=-0.434, P<0.05), respectively. The therapeutic effect of the observation group was better than the control group (P<0.05). Conclusion Kidney tonifying and brain strengthening acupuncture therapy can improve the effectiveness of sertraline in treating elderly depression, and its mechanism of alleviating depressive mood and cognitive function may be related to improving immune inflammation.