Apoptotic and/or ROS-induced DNA fragmentation in sperm cells may contribute to the development of male infertility. As the known dietary antioxidant, ascorbic acid prevents ROS production and protects sperm cells from DNA damage. Here, we found that ascorbic acid has the ability to inhibit DNase 1, one of the main endonucleases involved in DNA fragmentation during apoptosis. Site Finder and Molecular docking defined the ascorbic acid interactions with the most important residues of DNase 1, including H donor interactions with Asp 168 and Asn 170, and H-acceptor interaction with Asn 170. As a furan derivative, ascorbic acid could be considered a pioneer of substrate-based DNase I inhibitors. The results indicate to another possible mechanism for prevention of male infertility by ascorbic acid. (C) 2018 Elsevier Inc. All rights reserved.