The results indicated that acacetin (0.3–3 μM in vitro; 10 mg/kg in vivo) effectively attenuated Ang II-induced cardiomyocyte hypertrophy in vitro and abdominal aortic constriction-induced cardiac hypertrophy in vivo through activating the Sirt1/AMPK/PGC-1α pathway, indicating its potential for the prevention and treatment of cardiac hypertrophy. Here, PPARGC1A is linked to cardiac hypertrophy.