Objective To investigate the protective effect of Yulangsan Chalcone ( YLSC) on H9c2 cardiomyocyte injury induced by angiotensin II ( Ang II ) and its possible mechanism. Methods H9c2 cardiomyocytes were divided into blank control, model, and low-, medium-, and high-dose YLSC groups. After intervention with YLSC, the cells were induced with Ang II (1 μmol / L) to form an injury model. Cell viability was detected by cell counting kit-8 assay, autophagosomes were detected by monodansylcadaverine staining, reactive oxygen species were detected using the dichlorodihydrofluorescein diacetate fluorescence probe method, apoptosis was detected by Hoechst 33342 staining, and the ATP content was detected by enzyme-linked immunosorbent assay. Bcl-2 interacting protein 3 ( Bnip-3) and autophagy-related protein 5 ( Atg5) gene levels were detected by reverse transcription-polymerase chain reaction, and expression levels of the autophagy marker proteins p62, Beclin1, and microtubule-associated protein light chain 3 (LC3) II/ I were detected by Western blot. ResultsYLSC alleviated Ang II-induced H9c2 cardiomyocyte injury by enhancing cardiomyocyte viability(P<0. 05 or P<0. 01), promoting the formation of autophagosomes, and reducing the generation of reactive oxygen species(P<0. 01). YLSC also reduced cell apoptosis(P<0. 01), increased ATP levels in cells(P<0. 05 or P<0. 01), promoted the gene expression of Bnip-3 and Atg5(P<0. 05 or P<0. 01), and reduced the expression of p62 and increased the expression of Beclin1 and LC3II/ LC3I(P<0. 05 or P<0. 01). Conclusions YLSC can effectively inhibit Ang II-induced H9c2 cardiomyocyte injury and apoptosis, and its mechanism may be related to the initiation of myocardial autophagy, activation of autophagy-related factors, and clearance of apoptotic cells.