Abstract: Cognitive dysfunction refers to learning and memory dysfunction, visual spatial impairment, affective disorder in varying degrees after brain function impairment. Recent studies have shown that imbalance of epigenetic regulation plays an important role in cognitive dysfunction. As an important epigenetic modification, abnormal expression of histone lysine methylation may be an important molecular mechanism that leads to cognitive dysfunction. However, the concrete process has not been fully elucidated. Therefore, this review will focus on the role of histone lysine methylation in cognitive dysfunction.