Objective To verify whether sacubitril valsartan(S/V) can ameliorate the apoptosis level of hypoxic H9c2 cardiomyocytes by regulating mitochondrial dynamic system,and exert cardioprotective effects. Methods H9c2 cardiomyocytes were cultured and established a glucose oxygen deprivation model (OGD).The cells were divided into three groups:control group(CON), model group(OGD), S/V group(S/V). Apoptosis and reactive oxygen species (ROS) were detected by flow cytometry, mitochondrial membrane potential was detected by JC-1, and mitochondrial fusion protein 1(Mfn1), mitochondrial fusion protein 2 (Mfn2), dynamin related protein 1(Drp1), mitochondrial fission protein 1(FIS1), cytochrome c (CytC), B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein (Bax) and cysteinyl aspartate specific proteinase (Caspase-3) expression were detected by Western blotting (WB). GraphPad Prism 8 statistics was used for data analysis,multiple groups comparisons were conducted using one-way analysis of variance,and LSD-t test was performed for pairwise multiple comparisons. Results H9c2 cardiomyocytes were used to establish OGD cell model, and the morphology of cardiomyocytes was signifcantly improved by S/V treatment under light microscope. Flow cytometry analysis showed that S/V significantly reduced the level of intracellular ROS and inhibited cardiomyocyte apoptosis (P<0.05). Fluorescence microscope analysis showed that S/V significantly improved the level of mitochondrial membrane potential(P<0.05); WB showed S/V significantly increase the protein expression levels of Mfn2, mfn1 and Bcl-2, and reduce the protein expression levels of Drp1, FIS1, CytcC, Bax and Caspase-3 (P<0.05). Conclusion S/V may regulate mitochondrial homeostasis, reduce ROS production and cardiomyocyte apoptosis by promoting mitochondrial fusion and inhibiting mitochondrial division.