Histone acetylation is one of the epigenetic modifications. Histone acetylation, which is catalyzed by histone acetyltransferases and negatively regulated by histone deacetylases, plays an important role in a variety of cellular physiological and pathophysiological processes. Recent studies have shown that histone deacetylases are involved in a variety of pathophysiological responses to acute kidney injury, such as apoptosis, dedifferentiation, proliferation and regeneration. This article reviews the role and underlying mechanism of histone deacetylases in acute kidney injury induced by ischemia reperfusion, nephrotoxicants, sepsis and rhabdomyolysis.