Objective：To explore the protective effect of fibroblast growth factor 21（FGF21）on liver ischemia-reperfusion（IR）injury in mice and the possible mechanisms. Methods：Thirty C57BL/6 mice were randomly divided into 3 groups：sham-operated group，IR+NS group（mice were injected with 2 mL/kg saline by tail vein just before ischemia induction）and IR+FGF21 group（mice were injected with 2 mL/kg FGF21 before operation）. The mouse partial liver model of IR injury was established. Twelve hours after reperfusion，the mice were sacrificed and the serum and liver samples undergoing IR injury were collected. The ALT and AST levels in serum were determined. Liver histological damage was evaluated with hematoxylin-eosin（HE）staining and TUNEL detection. Levels of malondialdehyde（MDA），superoxide dismutase（SOD），glutathione（GSH）and reactive oxygen species（ROS）in liver tissue were also determined. Results：Liver tissues in IR+FGF21 group were more slightly damaged than those in IR+NS group（P < 0.01）. The ALT and AST levels in IR+FGF21 group were significantly lower than those of IR+NS group（P < 0.01）. The levels of plasma MDA and ROS contents in IR+FGF21 group were significantly lower than those of IR+NS group（P < 0.01）. The levels of plasma SOD and GSH in IR+FGF21 group were higher than those of IR+NS group（P < 0.01）. Conclusion：FGF21 can alleviate liver IR injury probably by inhibiting oxidant stress in mice.