Objective To investigate the effect of DRAM1 on the acute ischemic injury of H9C2 cardiomyocytes. Methods H9C2 cardiomyocytes were treated with Oxygen-glucose deprivation (OGD) after DRAM1 adenovirus transfection. MTT assay was performed to detect cell viability and Annex V/PI staining was used to analyze the cell apoptosis. Western blot was performed to measure the expression of P62. Results DRAM1 overexpression increased the H9C2 cardiomycytes viability after OGD treatment for 12 hours. DRAM1 overexpression was attenuated, while siRNA-AD-DRAM1 exacerbated the apoptosis rate of H9C2 cardiomycytes after OGD treatment for 12 hours by Annex V/PI staining. P62 protein expression was increased in the H9C2 cardiomycytes after OGD treatment for 12 hours, which was reversed by DRAM1 overexpression. Conclusion DRAM1 may protect H9C2 cardiomycytes against OGD injury due to the improvement of the autophagy flux.