Objective: To investigate the clinical efficacy of acupuncture combined with emotional intervention in patients with post-stroke depression (PSD). Methods: A total of 100 patients with PSD who met the inclusion criteria were randomly divided into an experimental group (50 cases) and a control group (50 cases) using the random number table method, and the enrollment was in order of admission time. The control group used conventional treatment of oral antidepressant Deanxit tablets (0.5 mg flupenthixol + 10 mg melitracen) with the dose appropriately adjusted according to the patient’s medication effect, and modern rehabilitation treatment given selectively according to the patient’s condition. The experimental group had similar treatment as the control group with the addition of traditional Chinese medicine (TCM) acupuncture combined with emotional intervention. The application effects of both groups before and after treatment were verified using the Hamilton Depression Rating Scale (Ham-D), National Institutes of Health Stroke Scale (NIHSS), and Activities of Daily Living (ADL), serotonin levels were measured, and statistical analyses were carried out. Results: The total effective rate of patients in the experimental group was significantly higher than that in the control group, and the Ham-D score, NIHSS score, ADL score, and serotonin level after treatment were significantly higher than those in the control group, and the difference between the two groups was statistically significant (P < 0.05). Conclusion: For patients with PSD, adding TCM acupuncture with emotional intervention on top of conventional treatment significantly improve the clinical efficacy and better improve the daily life ability of patients.