This article reviews (i) the component and process of protein acetylation system in cancers, including types of acetylation (N-acetylation, O-acetylation, and K-acetylation), regulators of acetylation (writers-acetyltransferases, erasers-deacetylases, acetyl coenzyme A, and readers), (ii) biological role of acetylation in cancer pathophysiology, including apoptosis, autophagy, cellular metabolism, cell cycle, proliferation, migration, and invasion, and (iii) acetylation system-based targeted drugs in cancer, including HAT inhibitors, HAT activators, HDAC inhibitors, and BET inhibitors. The gene discussed is HDAC9; the disease is cancer.