BACKGROUND The aim of the study was to investigate the effectiveness of alteplase intravenous thrombolysis combined with butylphthalide in patients with severe cerebral infarction. METHODS From February 2018 to March 2019, 100 patients with severe cerebral infarction in Rongcheng People's Hospital were recruited and randomly divided into two groups, i.e., alteplase intravenous thrombolysis treatment group and alteplase intravenous thrombolysis combined with butylphthalide treatment group. The efficacy of treatment methods was compared between the two groups by analyzing National Institutes of Health Stroke Scale (NIHSS) scores of patients on the first, seventh, and fourteenth days after treatment. Quality of life of patients was evaluated using Barthel scale before and after treatment, and also, the incidence of adverse reactions was compared between the two groups. RESULTS The therapeutic effect and quality of life in the alteplase intravenous thrombolysis combined with the butylphthalide group were better compared with patients in the alteplase intravenous thrombolysis group. The total effective rate of the alteplase intravenous thrombosis group was 80%, and that of the alteplase intravenous thrombosis combined with butylphthalide group was 100%; the latter treatment was more effective (p < 0.05). NIHSS scores of the patients at 1, 7, and 14 days after treatment were better in the former group than in the latter (p 0.05). In other words, the combination of drugs did not increase the incidence of adverse reactions. CONCLUSIONS Alteplase intravenous thrombolysis combined with butylphthalide in the treatment of severe cerebral infarction is safe, and may significantly improve patient's neurological function and quality of life without adverse reactions.