Sirtuins, class III HDAC, has originally been defined as a family of nicotinamide adenine dinucleotide-dependent enzymes. There are seven mammalian sirtuins (SIRTI07), which mainly deaceylate lysine residue on various proteins as a deacetylase. Sirtuins regulate a diverse array of biological processes, including DNA damage and repair, gene transcription regulation, apoptosis, metabolism and aging. In this research perspective we review the role and molecular mechanism of Sirtuin in DNA damage and repair.