p72 (probable ATP-dependent RNA helicase DDX17) belongs to the DEAD‑box RNA helicase family. p72 is important in RNA processing. Thus, the role of p72 in doxorubicin (DOX)‑induced cardiomyocyte injury was investigated in the present study. The changes in p72 expression levels were studied in cultured neonatal cardiomyocytes and p72 overexpression was induced using adenovirus vectors. To investigate the production of reactive oxygen species (ROS), dihydroethidium staining was conducted. TUNEL and Hoechst staining were used to indicate cell apoptosis. Microarrays were used to determine the altered expression of microRNAs. In DOX‑induced cardiomyocyte injury, the protein expression level of p72 was reduced. Overexpression of p72 protected cardiomyocytes from DOX‑induced ROS production and cell apoptosis. p72 reduced the activation of estrogen receptor α (ERα), thereby reducing DOX‑induced cell apoptosis. The present study indicated that p72 exerts a protective effect against DOX‑induced cell apoptosis via inhibition of ERα activation, indicating this may be a potential target of therapy for cardiac injury.