Postoperative cognitive dysfunction (POCD) is a common postoperative complication of the central nervous system that is common in elderly patients, especially in operation with greater trauma such as cardiac surgery and orthopedic surgery. POCD can lead to a decline in patients' attention, memory, orientation, and learning abilities after surgery, which is not conducive to postoperative recovery and may even affect their long-term quality of life. However, the pathogenesis of POCD has not been fully elucidated, and it is currently believed that central nervous system inflammation, oxidative stress response, blood-brain barrier disruption, neuronal apoptosis, and other factors may be the main causes of POCD. Histones can form nucleosomes together with DNA and are the main protein components of chromatin. Histone post-translational modification is a type of epigenetic modification that plays an important role in gene expression. In recent years, studies have shown that post-translational modifications of histones may be involved in the occurrence and development of POCD. This article reviews the research progress of histone post-translational modifications in POCD, providing new ideas for the prevention and treatment of POCD.