Apoptosis plays an important role in cardiac pathology, but the molecular mechanism by which apoptosis regulated remains largely elusive. Here, we report that miR-23a promotes the apoptotic effect of p53 in cardiomyocytes. Our results showed that miR-23a promotes apoptosis induced by oxidative stress. In exploring the molecular mechanism by which miR-23a promotes apoptosis, we found that it sensitized the effect of p53 on miR-128 regulation. It promoted the association of p53 to the promoter region of miR-128, and enhanced the transcriptional activation of p53 on miR-128 expression. miR-128 can downregulate prohibitin expression, and subsequently promote apoptosis. Our data provides novel evidence revealing that miR-23a can stimulate transcriptional activity of p53.