Abstract: Metabolic dysfunction-associated steatotic liver disease (MASLD), renamed from non-alcoholic fatty liver disease (NAFLD), is characterized by abnormal deposition of liver lipids. MASLD is characterized by abnormal lipid deposition in the liver, and its pathogenesis is closely related to insulin resistance (IR), lipid metabolism disorders, oxidative stress, and abnormalities of the intestinal and hepatic axes, there is no effective treatment for MASLD in the clinic. Silent information regulator 2 (SIRT2) is a nicotinamide adenine dinucleotide (NAD+)- dependent deacetylase, which is expressed in many organs such as the liver, and plays important physiological and pathological functions by interacting with different substrates. SIRT2 is expressed in several organs, including the liver, and exerts important physiopathological functions through interactions with different substrates. SIRT2 has been found to be involved in improving metabolic homeostasis, alleviating hepatic inflammation, and promoting liver regeneration. Moreover, some studies have shown that SIRT2 can delay the progression of MASLD. Based on this, this article presents a review of the research progress related to SIRT2 in the development of MASLD, aiming to explore the potential role of SIRT2 as a therapeutic target for MASLD.