Abstract： Objective： To observe the effect of acupuncture combined with mindfulness therapy on cognitive function and prognosis in patients with post-stroke depression (PSD). Methods ： A total of 80 cases of PSD patients were selected and divided into the control group and the observation group according to the random number table method，with 40 cases in each group. The control group was treated with mindfulness therapy， and the observation group was treated with acupuncture combined with mindfulness therapy. Both groups were continuously treated for eight weeks. Clinical effects were compared between the two groups. Changes in traditional Chinese medicine syndrome scores， Trait Anxiety Inventory (T-AI)，State Anxiety Inventory (S-AI)，and Self-rating Anxiety Scale (SAS)]，depression status [17-item Hamilton Depression Rating Scale (HAMD-17)，Patient Health Questionnaire-9 (PHQ-9)， and Self-rating Depression Scale (SDS)]，mindfulness levels [Mindful Attention Awareness Scale (MAAS)]， and cognitive function [Montreal Cognitive Assessment (MoCA)] were compared between the two groups before and after treatment. Results： The total clinical effective rate was 95.00% in the observation group and 80.00% in the control group， the difference being significant (P＜0.05). After treatment， traditional Chinese medicine syndrome scores of lack of energy， lack of interest， chest tightness and distention， sadness and crying，lack of appetite，irritability，insomnia and forgetfulness，bitter mouth and dry mouth in the two groups were decreased when compared with those before treatment (P＜0.05)，and the above eight traditional Chinese medicine syndrome scores in the observation group were lower than those in the control group (P＜0.05). After treatment， the scores of T-AI， S-AI， and SAS in the two groups were declined when compared with those before treatment (P＜0.05)，and the scores of T-AI，S-AI，and SAS in the observation group were lower than those in the control group (P＜0.05). After treatment，the scores of HAMD-17， PHQ-9， and SDS in the two groups were decreased when compared with those before treatment (P＜0.05)，and the scores of HAMD-17，PHQ-9，and SDS in the observation group were lower than those in the control group (P＜0.05). After treatment， the scores of MAAS and MoCA in the two groups were increased when compared with those before treatment (P＜0.05)， and the scores of MAAS and MoCA in the observation group were higher than those in the control group (P＜0.05). Conclusion： Acupuncture combined with mindfulness therapy can improve clinical symptoms of PSD， relieve anxiety and depression，enhance mindfulness level，restore cognitive function，and improve prognosis.