Background　Learning and memory are the basic functions of the brain, revealing their molecular mechanisms is of great importance. Recent studies show that epigenetic mechanisms play an important role in modulating learning and memory, of which the most common is histone acetylation and deacetylation, the balance between them serves as a key regulatory mechanism for learning and memory formation and maintenance. Histone deacetylation is regulated by histone deacetylases (HDACs).　Objective　To elucidate the function and relevant mechanisms of HDACs in regulating learning and memory and provide foundation for clarifying the molecular mechanisms of learning and memory, and provide new strategies for the treatment of learning and memory impairments in the end.　Content　The tissue sources, classifications, and molecular biological functions of HDACs are reviewed in this article. HDACs negatively regulates learning and memory, HDACs inhibitors can enhance synaptic plasticity and ameliorate learning and memory impairments.　Trend　In-depth study of the mechanisms of HDACs in regulating learning and memory not only helps to illustrate the mechanisms of learning and memory and their related diseases, but it also helps to provide possible therapeutic targets.