The role of miR-361-3p in the pathology of Alzheimer’s disease is unknown. The target scan was used to screen potential target genes of miR-361-3p, and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1) was emphasized. Results from western blotting and reverse transcription-quantitative polymerase chain reaction (RT-PCR) showed that down-regulated miR-361-3p was correlated with up-regulated BACE1 in Alzheimer’s disease patients’ brains. Luciferase assay confirmed that miR-361-3p directly targets BACE1. MiR-361-3p overexpression and knockdown experiments were performed and found that miR-361-3p could regulate the expression of BACE1, and the accumulation of APP-β in APPswe transfected SH-SY5Y cell. A Morris water maze test was performed and showed that overexpression of miR-361-3p improved cognitive deficits in APP/PS1 mice. We found miR-361-3p inhibited β-amyloid accumulation by targeting BACE1, which thus weakened cognitive deficits in Alzheimer's disease.