6`-O-galloylpaeonifl orin (GPF) is a galloylated derivate of paeonifl orin and a key chemical constituent of the peony root, a perennial fl owering plant that is widely used as an herbal medicine in East Asia. This study is the fi rst investigation of the cytoprotective effects of GPF against hydrogen peroxide (H2O2)-induced cell injury and death in human HaCaT keratinocytes. GPF demonstrated a signifi cant scavenging capacity against the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical, H2O2-generated intracellular reactive oxygen species (ROS), the superoxide anion radical (O2 -), and the hydroxyl radical (?OH). GPF also safeguarded HaCaT keratinocytes against H2O2-provoked apoptotic cell death and attenuated oxidative macromolecular damage to DNA, lipids, and proteins. The compound exerted its cytoprotective actions in keratinocytes at least in part by decreasing the number of DNA strand breaks, the levels of 8-isoprostane (a stable end-product of lipid peroxidation), and the formation of carbonylated protein species. Taken together, these results indicate that GPF may be developed as a cytoprotector against ROS-mediated oxidative stress.