Although USP20 has been extensively studied in pathological processes, particularly in cancer biology.[22, 23, 51] Its function in cardiac protection has only been explored recently.[25, 26, 52] Consistent with our findings, recent study indicated that constitutive knockout of USP20 exacerbates pressure overload‐induced cardiac hypertrophy in TAC model.[52] We employ cardiomyocyte‐specific USP20 knockout and overexpressed mice to elucidate the function and mechanisms of USP20 in vivo. This evidence concerns the gene USP20 and cardiac hypertrophy.