Silent information regulator 1 (SIRT1) is a kind of nicotinamide adenosine dinucleotide (NAD+)-dependent histone deacetylase, which is involved in the cell survival, aging, apoptosis, cell metabolism, and protective effect in aging-related diseases and organ damage. The increased SIRT1 signaling transduction in heart could mediate the regulation of related-downstream signaling molecules to reduce oxidative stress, apoptosis, and inflammatory responses in myocardial ischemia/reperfusion (I/R) injury. This article introduce the basic characteristics, expression and activation regulatory mechanisms of SIRT1, and review the protective effect and related mechanism of SIRT1 in myocardial I/R injury. Stimulation of endogenous SIRT1 or Sirtuins is expected to be a new target in the prevention of myocardial I/R injury.