The tender leaves and buds of Vaccinium dunalianum Wight have been traditionally processed as folk tea, known as Que Zui tea (QT), with a wide range of benefits to humans. In this study, Que Zui tea hot-water extract (QTW) and aqueous-ethanol extract (QTE) were tested for their effectiveness to alleviate acetaminophen (APAP)-induced liver damage. QTW and QTE significantly inhibited the alanine aminotransaminase, aspartate aminotransaminase, tumor necrosis factor-α, interleukin-6, and interleukin-1β levels in the serum. Both extracts also ameliorated pathological damage and inhibited oxidative stress in the liver of APAP-induced mice. In addition, QTW and QTE activated the nuclear erythroid related factor 2 signal pathway, and inhibited mitogen-activated protein kinase activation. QTW and QTE also suppressed hepatocyte apoptosis by improvement of Bcl-2/Bax and inhibition of caspase-3 and caspase-9 expression. The results demonstrated that QTW and QTE could effectively protect APAP hepatotoxicity, which might be attributed to their antioxidant, anti-inflammatory and anti-apoptosis activities.