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Background: This study aims to check the effect of hirudin on serum matrix metalloproteinase-9 (SMMP9) in patients with acute cerebral infarction (ACI). Methods: For acquisition of obtained data of included studies, we will undertake comprehensive search from the following electronic databases: MEDLINE, Embase, Cochrane Library, CINAHL, WANGFANG database, VIP database, CBM database, and China National Knowledge Infrastructure from their inceptions to the March 31, 2020. No restrictions of language and publication status will be applied to all database sources. Two investigators will independently undertake study selection, data extraction, and study quality. Any different opinions between 2 investigators will be solved by a third investigator through consultation. Study quality will be assessed using Cochrane risk of bias tool, and level of evidence for outcome results will be identified using the Grading of Recommendations Assessment, Development, and Evaluation method. We will use RevMan 5.3 software for statistical analysis. Results: From this study, we will evaluate the effect of hirudin on SMMP9 in patients with ACI. Conclusion: The findings of this study will provide evidence to ensure the effect of hirudin on SMMP9 in patients with ACI.