Objective To explore the effect of continuous intervention based on multidisciplinary team collaboration in elderly patients with post-stroke depression. Methods A total of 106 elderly patients with post-stroke depression who were admitted to our hospital from November 2017 to January 2019 were randomly divided into a study group （53 cases） and a control group （53 cases）. The control group was given routine inhospital medical care measures and discharged health guidance. In addition to this， the study group was given continuous intervention based on multidisciplinary team collaboration. Differences in quality of life， depression， dysfunctional status， stress response， compliance， and satisfaction were compared between the two groups before and after the intervention. Results After the intervention， the two groups' World Health Organization Quality of Life （QOL-BREF） scores were significantly higher than before the intervention， and the study group was higher than the control group （P ＜ 0.01）； the Hamilton Depression Scale （HAMD）， Adrenocorticotropic Hormone （ACTH）， Cortisol （Cs） in the two groups were significantly lower than those before intervention， and the study group was lower than those in the control group （P＜ 0.01）； the values of Dysfunction Assessment Scale （DAS） factors of the two groups were significantly higher than those before the intervention， and the research group was higher than those of the control group （P ＜ 0.01）. Conclusions Continuous intervention based on multidisciplinary team collaboration can effectively alleviate the psychological stress response of post-stroke depression， improve the depression and dysfunction conditions and improve patients' quality of life.