Calcific aortic valve disease (CAVD) is characterized by thickening and calcification of the aortic valve, which can develop into valve sclerosis, and rapidly progress to a series of abnormal hemodynamic changes, and eventually heart failure and death. Aortic valve interstitial cells, as the main cell population of aortic valve, play a key role in the development of CAVD. The development of technologies such as single cell sequencing has improved researchers’ understanding of the origin, phenotype and functional heterogeneity of interstitial cells. This article reviews the role of interstitial cell heterogeneity in calcified aortic valve disease, which may provide a new idea for targeting interstitial cells to attentuate CAVD process.