Abstract Body: Hypertrophic cardiomyopathy (HCM) is a common heart disease characterized by myocardial hypertrophy and is also the most common genetic heart disease. Although the pathogenic mechanism of gene mutations in HCM has been understood in the past few decades, especially mutations in genes encoding sarcomere proteins such as MYH7 and MYBPC3, more than 50% of clinically diagnosed HCM patients do not have sarcomere gene mutations. These cases are unlike typical monogenic diseases. However, regardless of the reasons for inducing myocardial hypertrophy, their common feature is an increase in myocardial cell volume, which requires the synthesis of a large amount of protein to meet the need for increased myocardial cell growth. Our recent research suggests that a new class of genes, RNA Pol III-dependent genes, are upregulated in hypertrophic myocardial tissue. The results of ISO and surgical induced myocardial hypertrophy models of mice show a significant increase in RNA Pol III-dependent gene transcription. The tissue culture experiment also demonstrated that ISO could stimulate RNA Pol III gene expression. Transcription factor, Brf1 (TF IIB-related factor 1) specifically regulates RNA Pol III-dependent gene transcription. Interestingly. Brf1 is generally elevated in tissues of myocardial hypertrophy of the cases. These new findings provide a new direction for us to further explore the mechanism of myocardial hypertrophy. More studies on the mechanisms of myocardial hypertrophy are going on.