To explore the effect of microRNA-455-5p (miR-455-5p) and Cytokine Signaling-3 (SOCS3) expression, a model of the cell damage induced during myocardial infarction was established using H₂O₂. The cell counting Kit-8 (CCK-8) and quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) assays were used to detect the cell viability and the expression of miR-455-5p and SOCS3 in cells cultured with different concentrations of H₂O₂. After the selection of the optimum culture concentration, a dual-luciferase reporter gene assay was used to detect the binding between and miR-455-5p and its potential target SOCS3. SOCS3 siRNA was transfected into cardiomyocytes using chitosan nanoparticles as a gene carrier, which led to the knockdown of SOCS3 expression, and the cells were transfected with miR-455-5p mimics and inhibitors. The expression of cardiac protective proteins was detected by western blotting, cell viability was detected by CCK8, and cell apoptosis was detected by flow cytometry. The aim of this study was to investigate the effect of miR-455-5p and SOCS3 expression on the activity and apoptosis of damaged cardiomyocytes, and to identify any protective effect on cardiomyocytes. Finally, after the simultaneous overexpression of SOCS3 and miR-455-5p, and the expression of cardiac protective proteins, cell activity, and apoptosis rate were detected. The results showed that the expression of miR-455-5p decreased in a concentration-dependent manner and that the expression of SOCS3 increased in a concentration-dependent manner when the cells were cultured in different concentrations of H₂O₂. The knockdown of SOCS3 expression promoted an increase in cell activity, an increase in cardiac protective proteins, and a decrease in apoptosis. The upregulation of miR-455-5p significantly inhibited the expression of SOCS3, increased cell activity, inhibited apoptosis, and exerted protective effects in myocardial cells. The overexpression of SOCS3 reversed the inhibition of SOCS3 by miR-455-5p and reduced the protective effect of miR-455-5p on myocardial cells. Therefore, this study showed that the upregulation of miR-455-5p significantly inhibited the expression of SOCS3 and resulted in the increased protection of cells damaged by H₂O₂, which was used as a model of myocardial infarction. These results indicate the potential of miR-455-5p in myocardial protection, suggesting that miRNA may be a resource for myocardial therapy.