Objectives To explore the characteristics and correlation of serum TNF-α levels and cognitive function before and after treatment in patients with post-stroke depression. Methods A total of 42 patients with post-stroke depression in the inpatients and outpatients department of Suzhou Guangji Hospital from July 2016 to June 2019 were recruited as study group retrospectively. And 42 age matched social health examinees were selected as the control group. The patients in the study group were treated with conventional oral antidepressants. According to the specific situation of the patients， the dosage gradually increased to the treatment amount within 1-2 weeks.In the study group， before treatment and 8 weeks after treatment， the severity of depression was assessed by Hamilton Depression Scale （HAMD）， the cognitive function was tested by rapid visual information processing （RVP） in Cambridge Neuropsychological Automated Test（CANTAB）， and the serum TNF-α concentration was measured by enzyme-linked immunosorbent assay.In the control group， cognitive function and fasting serum TNF-α were measured only at baseline， and the indexes of the two groups and the indexes before and after treatment in the study group were compared.Pearson correlation analysis was used to study the correlation of TNF-α level with RVP cognitive test and HAMD-17 total score before and after treatment in the study group. Results （1） Before treatment， the serum TNF-α level in the study group （35.80±7.06） ng/L was higher than that in the control group（20.70±3.65） ng/L； in the cognitive test， the RVP hit rate（56.33±20.89）， the total correct number（244.73±14.38）， the total number of hits （14.57±5.05） and A' statistics （0.88±0.05） were lower than those in the healthy control group， while the total number of missed strokes in the study group（11.39±4.55） was higher than that in the control group （7.29±4.02）， and the difference was statistically significant （P ＜ 0.05）. The result of correlation analysis showed the serum TNF-α levelin the study group was negatively correlated with the hit rate （r=-0.271）， total correct number（r=-0.345）， total number of hits （r=-0.317） and A′statistics （r=-0.351） in the RVP （P＜ 0.01）， and was positivelyrelated to the total missed number（r=0.420） and HAMD-17 （r=0.756）（P＜ 0.01）. （2） After treatment， the serum TNF- αlevel， RVP cognition test （total correct number， total number of hits， A′statistic） and total HAMD-17 scores in the study group were （22.30±4.04） ng/L， （253.01±15.63）， （18.58±4.79）， （0.90±0.06） and （7.52±2.12）， which were all improved， and the differences were statistically significant （all P＜ 0.05）. Conclusions Serum TNF-α increases and cognitive function decreases in patients with post-stroke depression. Serum TNF-α decreases and cognitive function improves after treatment. Correlation analysis suggests that serum TNF-α levels are related to cognitive function in patients with post-stroke depression.