Aim To explore the effects of a novel H2S donor (8L) on oxidative stress-induced damage and the mechanisms underlying NF-E2-related factor 2 (Nrf2) in H9c2 cardiomyocytes. Methods H9c2 cardiomyocytes were treated with exogenous reactive oxygen species, hydrogen peroxide (H2O2), to set up an oxidative injury to mimic the in vitro status induced by acute myocardial ischemia-reperfusion. Prior to the treatment with H2O2, the cells were treated with 8L and then its protective action was investigated. In order to test the roles of Nrf2, its selective inhibitor brusatol (BR) was used before H2O2 or 8L. Cell counting kit-8 was used to measure cell viability. Lactate dehydrogenase (LDH) release was assessed by a commercial kit, mitochondrial membrane potential (MMP) was observed by rhodamine 123 staining followed by photofluorography and nuclear Nrf2 expression was examined by Western Blot assay. Results