The aim of this study was to observe the initiation timing of donepezil hydrochloride in the treatment of post-stroke cognitive impairment (PSCI). Methods: One-hundred and twenty patients with PSCI were recruited and divided into early treatment group (course < 3 months) and late treatment group (course 3~6 months), 60 cases per group. All the cases were treated with donepezil hydrochloride for 6 months. The mini-mental state examination (MMSE), montreal cognitive assessment (MoCA) and clinical dementia rating (CDR) were used to scoring patients at beginning of treatment and 1, 3 and 6 months after treatment. Re? sults: To compare the baselines of two groups, the MMSE and MoCA scores in the early treatment group were significantly higher than those in the late treatment group (P<0.05), and the CDR scores in two groups have no statistical difference (P>0.05). At 1, 3 and 6 months after treatment, the MMSE score, MoCA score and CDR score of the two groups were better than those before treatment. The total effective rate of MoCA score, the proportion of people with increased MMSE score in the early treatment group were significantly higher than those in the late treatment group (P<0.05). The proportion of people with decreased CDR score in two groups have no statistical difference (P>0.05). Conclusion: Treat PSCI with donepezil hydrochloride early is better than late.