Our results demonstrate that the inhibition of p53 with siRNA attenuates autophagic cell death and myocardial infarction sizes in the heart with I/R injury, while overexpression of p53 enhanced H2O2-induced autophagic cell death and inhibition of autophagy with 3-MA blocked this response in cardiomyocytes. The gene discussed is TP53; the disease is myocardial infarction.