Objective: To investigate the differential of protein expression in CCl4 induced mice treated with lycorine. Methods: The present study was carried out to identify the differentially expressed protein in carbon tetrachloride (CCl4) induced oxidative stress mice treated with lycorine (5 mg/kg. bw) using 2D gel and MALDI-TOF. Results: We observed many kinds of differentially expressed protein in experimental liver. Among these, three are much differently expressed protein which is identified as ATP synthase, regucalcin and HSP60; these proteins are involved in the ATP synthesis, calcium regulation and rescue the integrity cellular proteins respectively. Conclusion: This investigation provided a molecular mechanism of the lycorine during CCl4 induced oxidative stress in mice liver.