During the occurrence and development of various heart diseases, continuous deterioration of myocardial fibrosis leads to remodeling and dysfunction of the cardiac structure. As a newly discovered mechanically sensitive ion channel, Piezo1 has opened up a new field of research on cellular mechanical transduction. Piezo1 combines a fine force transducer with Ca2+ influx and participates in the regulation of cellular mechanical transduction, thereby regulating cellular biological functions. Recent studies have shown that the biomechanical changes induced by myocardial injury regulate the expression of Piezo1 in cardiomyocytes and cause an imbalance in calcium homeostasis, which plays an important role in the positive feedback loop of myocardial fibrosis. This review summarizes the theoretical basis and related studies of Piezo1 in regulating cardiac fibrosis and suggests that the Piezo1 channel may become a new target for the treatment of cardiac fibrosis, thereby providing a new research horizon for the prevention and treatment of cardiac fibrosis.