Acute myocardial infarction is caused by continuous ischemia and hypoxia of myocardial cells, leading to myocardial cell necrosis. Reperfusion therapy is the standard strategy for reducing infarct size and improving the prognosis of myocardial infarction. However, myocardial injury caused by reperfusion therapy is accompanied by various pathophysiological processes, such as oxidative stress, inflammatory response, myocardial fibrosis, extracellular matrix remodeling, etc. Transcription factor EB (TFEB) is a central regulatory factor in the autophagy-lysosome signaling pathway, involved in signaling pathways such as stress response, myocardial energy metabolism, autophagy, and lysosomal biogenesis. It is closely related to the repair of myocardial injury after myocardial infarction. This review aims to elucidate the mechanism of TFEB in myocardial ischemic injury.