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Objective To observe the effects of interactive scalp acupuncture on cognitive function, depression, anxiety and sleep quality in patients with post-stroke patients. Methods A total of 445 patients with stroke who had been admitted to the Rehabilitation Department of Nan'ao People's Hospital, Shenzhen Second People's Hospital and Shenzhen Futian District Hospital of Traditional Chinese Medicine from May 2019 to May 2020 were selected and randomly divided into the experimental group (n=223) and the control group (n=222), with 23 cases shed in the experimental group and 22 cases shed in the control group. Two groups of patients were treated with standard care and conventional rehabilitation exercise therapy. The experimental group was given interactive head acupuncture therapy, while the control group was given conventional scalp acupuncture and cognitive training therapy for a course of 8 weeks. Before the initial treatment, at the end of the treatment course, and at the follow-up 2 months later, Montreal Cognitive Assessment Scale (MoCA), Mini-mental State Examination (MMSE), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Pittsburgh Sleep Quality Index (PSQI), and Modified Barthel Index (MBI) were evaluated. The levels of serum Brain-derived Neurotrophic Factor (BDNF) and Nerve Growth factor (NGF)were measured before and after the first treatment. Results At the end of the treatment course and at the follow-up, the scores of MoCA, MMSE and MBI in the experimental group were increased compared with those before treatment (P＜ 0.01), and the scores of HAMD, HAMA and PSQI were decreased compared with those before treatment (P＜ 0.01). MoCA scores increased (P＜ 0.01) and HAMD scores of the control group decreased (P＜ 0.01) both at the end of the treatment course and at the follow-up, whereas MMSE and MBI scores of the control group increased only at the end of treatment (P< 0.01). The scores of MoCA, MMSE and MBI in the experimental group were higher than those in the control group at the end of the course and at the follow-up (P＜ 0.01), and the scores of HAMD, HAMA and PSQI in the experimental group were lower than those in the control group (P＜ 0.01). In terms of serological indexes, the levels of BDNF and NGF in both groups at the end of the course of treatment were higher than those before treatment (P＜ 0.01), and those in the experimental group were higher than those in the control group (P< 0.01). Conclusion Interactive scalp acupuncture can significantly improve not only the cognitive function, depression, anxiety but also the sleep quality and self-care ability of patients with stroke, and promote the recovery of cerebral nerve function. Compared with conventional rehabilitation treatment, it has the efficacy advantage which can be maintained after stopping the treatment. [ABSTRACT FROM AUTHOR]