Objective. To evaluate the hepatoprotective mechanism of Xwak granule (Xwak) in treatment of mice with alcoholic liver injury via activating ERK/NF-kappa B and Nrf/HO-1 signaling pathways.Methods. The chemical composition of Xwak was tested by liquid chromatography coupled with mass spectrometry (LC-MS). Herein, 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical tests were performedin vitro. The hepatoprotective effect of Xwak was assessed at different concentrations (1.5, 3, and 6 g/kg) in a mouse model of alcoholic liver injury.Results. Totally, 48 compounds, including 16 flavonoids, 8 tannins, 9 chlorogenic acids, and 15 other compounds, were identified from Xwak. Xwak showed to have a satisfactory antioxidant activityin vitro. In a group of Xwak-treated mice, the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were decreased compared with a group of the mouse model of alcoholic liver injury. In addition, the levels of antioxidant enzymes, such as glutathione peroxidase (GSH-PX), total superoxide dismutase (T-SOD), and catalase (CAT), were noticeably increased and the levels of malondialdehyde (MDA), tumor necrosis factor-alpha(TNF-alpha), transforming growth factor-beta(TGF-beta), and interleukin-6 (IL-6) were markedly reduced in the liver of mice. The state of oxidative stress in the mouse model of alcoholic liver injury was improved after treatment with Xwak. The improvement of inflammation-mediated disruption may conducive to the Xwak activity in the control of liver injury. The signals of p-ERK1/2, p-NF-kappa B, COX-2, iNOS, CYP2E1, Nrf, and HO-1 were significantly induced in the liver of mice after treatment with Xwak.Conclusions. The abovementioned findings indicated that the hepatoprotective mechanism of Xwak could be achieved by activating ERK/NF-kappa B and Nrf/HO-1 signaling pathways to alleviate oxidative stress and inflammatory.