We aimedto detect whether the effect of apigenin (Apig) on themyocardial infarction-induced cardiomyocyte injury of mouse myocardial cells and acute myocardial infarction (AMI) mice was through regulating Parkin expression via miR-103-1-5p. The myocardial infarction cardiomyocyte model (Hypoxia/reoxygenation) was first constructed, then the mouse myocardial cells were treated with Apig, and the expression of miR-103-1-5p was decreased and the expression of Parkin was increased by qRT-PCR and Western blot. It was confirmed by miRNA pulldown and luciferase reporter system that miR-103-1-5p in mouse myocardial cells can bind to Parkin mRNA and inhibit Parkin expression.Next, a lentiviral vector silenced Parkin and overexpressingmiR-103-1-5pwas constructed and transfected into Apig-treated cells. Autophagy was detected by mitochondrial autophagy marker proteins [atypical protein kinase C (aPKC)-interacting protein (p62) and bcl-2/Adenovirus E1B 19-kd interacting protein 3 (BNIP3)] viaWestern blot, mitochondrial function was detected by JC-1 probe, and apoptosis was detected by flow cytometry. It was confirmed that Apig regulated mitochondria autophagy through miR-103-1-5p and Parkin, which ultimately affected cardiomyocyte death. Finally, an AMI mouse model was constructed, and then the mice were treated with Apig. The infarct size was detected by triphenyl tetrazolium chloride (TTC) staining, and the Apig relieved the myocardial infarction. The expression of miR-103-1-5p was decreased and the expression of Parkin was increased by qRT-PCR andWestern blot. The above results simplified that the cardio protection of Apig and miR-103-1-5p against injury of myocardial infarction cardiomyocyte by targeting Parkin. These results provided a novel treatment againstmyocardial infarction cardiomyocyte.