Histone phosphorylation is a kind of post-translational modifications，which belongs to the regulation of epigenetics. It was found to play an important role in DNA repair and cell division. In recent years，more and more studies have shown that it also regulates cognitive function such as learning and memory. Here，we reviewed recent findings about the role of histone phosphorylation in learning and memory，as well as the molecular mechanisms for its upstream signal pathways and downstream regulation in transcription to provide new theoretical basis and therapeutic targets at cognitive disorders.