Abstract: Objective To investigate the effects of curcumin on heart development-related genes GATA4, MEF2C and Nkx2.5, and to explore the epigenetic regulation mechanism. Methods Neonatal mouse cardiocytes were treated with curcumin with different concentration and different time. ELISA was used to detect the histone acetylase (HATs) activity of cardiocytes, western blot to detect the acetylation of histone H3, real time RT-PCT to measure the expression of heart development-related genes GATA4, MEF2C and Nkx2.5, and chromatin immunoprecipitation (ChIP)-PCR to analyse the chromatin struction. Results 30mol/L of curcumin could inhibit the HAT activity and the acetylation of histone H3 at 24 hours. Accordingly the expression of GATA4, MEF2C and Nkx2.5 were repressed significantly (P<0.05). The result of ChIP-PCR showed that the the acetylation of histone which bound with promoter regions of these genes were reduced. Conclusion Curcumin could inhibit the HAT activity and repress the expression of heart development-related genes GATA4, MEF2C and Nkx2.5 effectively. And the loose structure of chromatin induced by hypoacetylation of histone bound with promoter regions might be one mechanism of this effect.