A vital finding is that we found tempol treatment in APAP-induced acute hepatotoxicity mice normalizes liver function mainly via activating PI3K/Akt/Nrf2/HO-1 pathway, which results in anti-oxidative stress and anti-apoptotic effects, suggesting a potential treatment with tempol to APAP-induced acute liver injury. This evidence concerns the gene NFE2L2 and hepatotoxicity.