Abstract: Histone deacetylases (HDACs) are a class of key enzymes that regulate epigenetics. There are 5 small-molecule HDACs inhibitors having been approved for anti-cancer therapy on the market. In recent years, there have been more and more studies on the antiviral aspects of HDACs inhibitors. This article classifies viruses into human immunodeficiency virus 1 (HIV-1), new coronavirus (SARS-CoV-2), Epstein-Barr virus (EBV) and other viruses, systematically summarizes the recent advances of antiviral effects of the HDACs inhibitors from the perspective of medicinal chemistry. This review aims to provide the researchers the convenience of accessing the latest advances of the antiviral effects of HDACs inhibitors, and to analyze the challenges and prospects of this field in future drug discovery.