Objective:To observe the clinical efficacy of Xinyue Decoction combined with fluoxetine hydrochloride in the treatment of cognitive impairment of senile depression.Methods:A randomized controlled trial study was conducted. Totally 116 elderly patients with depression accompanied by cognitive impairment were set as observation subjects, and were divided into a control group and an experimental group using random number table method, with 58 patients in each. The control group received treatment with fluoxetine hydrochloride capsules, while the experimental group was administered Xinyue Decoction Granules in addition to the treatment regimen of the control group. The treatment lasted for 8 weeks for both groups. Comparison was made between the two groups regarding the changes in TCM syndrome scores. Hamilton Depression Scale (HAMD-24) was used to assess the degree of depression, and Montreal Cognitive Assessment (MoCA BJ) was used to assess cognitive ability; the serum levels of brain-derived neurotrophic factor (BDNF), IL-1β, IL-6 and TNF-α were detected by ELISA; the adverse reactions during treatment were observed and recorded, and the clinical efficacy was evaluated.Results:The total effective rate of TCM syndromes was 90.4% (47/52) in the experimental group and 75.5% (40/53) in the control group, with statistical significance ( χ2=4.11, P<0.05); the total effective rate of MoCA-BJ was 76.9% (40/52) in the experimental group and 58.5% (31/53) in the control group, with statistical significance ( χ2=4.61, P<0.05); the total effective rate of HAMD-24 was 88.5% (46/52) in the experimental group and 71.7% (38/53) in the control group, with statistical significance ( χ2=4.07, P<0.05). After treatment, the TCM syndrome score, HAMD-24 and MoCA-BJ scores of the experimental group were lower than those in the control group ( t=-3.51, -5.11, 2.39, P<0.01 or P<0.05); the level of serum BDNF [(10.49±1.76) ng/L vs. (9.61±1.85) ng/L, t=2.28] in the observation group was higher than that of the control group ( P<0.05), and the levels of IL-1β, IL-6 and TNF-α were lower than those in the control group ( t=-2.50, -2.46, -2.18, P<0.05). During the treatment, the incidence of adverse reactions was 5.77% (3/52) in the experimental group and 7.55% (4/53) in the control group, without statistical significance ( χ2=0.13, P>0.05). Conclusion:Xinyue Decoction combined with fluoxetine hydrochloride can reduce the degree of depression in elderly patients with cognitive impairment of depression, improve the cognitive ability of patients and clinical efficacy.