Histone acetylation attracts more attentions due to its important biological functions among various histone modifications. It takes place under the catalysis the histone acetyltransferase (HAT) using acetyl coenzyme A as acetyl-group donor. Because the aberrant expression of histone acetylation is closely related to a series of diseases including diabetes, cancer, neurological disorders, cardiovascular diseases, chronic inflammation and HIV, the detection of HAT activity is of great significance to the discovery, prevention and treatment of diseases. In this paper, the detection strategies for HAT activity in recent six years are reviewed, with emphasis on the research progress of HAT detection methods combined with fluorescent, electrochemical, electrochemiluminescent and photoelectrochemical technology. In addition, the current challenges and future prospects of HAT activity monitoring are discussed.