The article not only systematically summarises the biogenesis, degradation, function and mechanism of PIWI‐interacting RNAs (piRNAs), but also emphasises the research progress of piRNAs in the treatment of various CVDs, including myocardial infarction (MI), hypertrophic cardiomyopathy (HCM) and heart failure (HF), etc. The potential of targeting piRNA in the treatment of CVDs and its application as a biomarker of CVDs are discussed. The gene discussed is PIWIL4; the disease is myocardial infarction.