Abstract: Shaoyao Ruangan Heji (SYRG), a liquid pharmaceutical formulation of traditional Chinese medicine, has been used clinically for the prevention and treatment of chemotherapy-induced liver injury in Zhejiang Cancer Hospital (China) for 37 years. However, its underlying therapeutic mechanism is still unclear. Because oxidative stress is a crucial etiological factor implicated in the pathology of chemotherapy-induced liver injury, in this study, the protective effect of SYRG on carbon tetrachloride (CCl4)-induced oxidative stress and liver injury in mice were evaluated and its mechanisms were investigated by Mouse Stress and Toxicity Pathway Finder PCR Array. The results showed that pretreatment with SYRG significantly attenuated CCl4-induced liver damage in mice, evidenced by decreased serum enzyme activities of ALT and AST, which was also supported by the histopathological examination of the mice liver. The SYRG also showed a significant protective effect against CCl4-induced hepatic MDA elevation and depletion of T-AOC, SOD and GSH content. Furthermore, SYRG regulated 25 genes related to six stress and toxicity pathways (Oxidative stress, hypoxia, cell necrosis, inflammatory response, DNA damage signaling and heat shock proteins/unfolded protein response) in the impaired liver induced by CCl4. These results indicated that SYRG has protective effects against CCl4-induced liver injury and its underlying mechanisms involve the modulation of multiple stress and toxicity pathways. These findings would be beneficial for understanding of the therapeutic effects of SYRG in treatment of chemotherapy-induced liver injure in clinic.