OBJECTIVE: To investigate the effects of butylphthalide on cognitive function and serology indexes of patients with acute cerebral infarction (ACI), and to analyze their relationship. METHODS: 88 ACI patients from our hospital during Jul. 2014 to May 2015 were divided into control group (n=38) and observation group (n=50) according to random number table. Control group was given Aspirin enteric-coated tablets 100 mg (initial dose of 300 mg), po, qd, and routine treatment as oxygen inhalation, fluid replacement. Observation group was additionally given Butylphthalide capsules 0.2 g, po, tid. Both groups received treatment for 1 month. MMSE score and serology indexes (Hcy, MMP-9, 6-k-PGF1a, NSE) of 2 groups were observed, and the relationship of MMP-9, 6-k-PGF1a, NSE with MMSE score in observation group were analyzed after treatment. The occurrence of ADR was recorded. RESULTS: After treatment, MMSE score and 6-k-PGF1a level of observation group were significantly higher than those of control group; MMP-9 and NSE levels of observation group were significantly lower than those of control group; with statistical significance (P<0.05). MMP-9 and NSE showed significantly negative correlation with MMSE score in observation group, and 6-k-PGF1a showed significantly positive correlation with MMSE score. There was no statistical significance in the incidence of ADR between observation group (16.0%) and control group (18.4%) (P>0.05). CONCLUSIONS: Butylphthalide can significantly improve cognitive function in ACI patients with good safety. The expression of MMP-9, NSE and 6-k-PGF1a in serum may be associated with the cognitive function injury.