Aim To investigate the protective effects of quercetin on H9c2 cells injury induced by nutritional deprivation, and observe its effect on adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signalling pathway. Methods H9c2 cells were cultured in vitro and divided into five groups:control group, nutritional stress group (NS group), quercetin group (NS+Qu group), compound C group (NS+CC group), and quercetin+compound C group (NS+CC+Qu group). The viability of H9c2 cells was determined by CCK8 assay and Hoechst staining. The apoptosis and mitochondrial membrane potentials of H9c2 cells were measured using flow cytometry. ATP content in H9c2 cells were observed. Western blot was used to detect the expression levels of Cleaved caspase-3, PTEN induced putative kinase 1 (PINK1), mitofusin2 (MFN2) and p-AMPK in H9c2 cells. Results Compared with control group, the viability of H9c2 cells in NS group was significantly decreased (P<0.05), the apoptotic rate and Cleaved caspase-3 expression were greatly increased (P<0.05), ATP level, mitochondrial membrane potentials (AMRE) and PINK1 expression were significantly decreased (P<0.05). Compared with NS group, the viability of H9c2 cells in NS+Qu group was significantly increased (P<0.05), the apoptotic rate and Cleaved caspase-3 expression were greatly decreased (P<0.05), ATP level, mitochondrial membrane potentials (AMRE) and PINK1 expression were significantly increased (P<0.05). Compared with NS+Qu group, the viability of H9c2 cells and p-AMPK expression level in NS+CC+Qu group was significantly decreased (P<0.05). Conclusion Quercetin can improve the injury of H9c2 cells via regulating AMPK signaling pathway.