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. This evidence concerns the gene PIWIL1 and myocardial infarction.