Abstract: Abstract　Objectives: To observe the anticancer effect of hirudin on H22 tumor cells in mice and to explore its mechanism of action. Methods: After H22 hepatoma cells were injected into the right anterior axillary fossa of 40 mice, they were randomly divided equally into 4 groups: the high-dose hirudin group ( 2.0 g/kg; Group C ), low-dose hirudin group ( 1.0 g/kg; Group D ), the positive control ( 20 mg/kg 5-fluorouracil intraperitoneally; Group B ), and the negative control ( 0.1 mL/10 g physiologic saline; Group A ). At 14 days after administration, the tumors were taken out and weighed, and then the inhibitory ratio was calculated. The tumor tissue slices were stained using the immunohistochemistry. The mean OD density was measured using Image-Pro Plus 6.0 image analysis software to determine C-met expression in the tumors. Results: The inhibitory action of hirudin was observed in Groups A and B. The inhibition rates were 37.63% and 23.71% in the two hirudin treatment groups, respectively, with significant differences compared with Group D ( P < 0.01, P < 0.05 ). The trial shows that C-met expression was significantly decreased in the high-dose and low-dose hirudin groups compared with the negative control ( P < 0.05 ). Conclusion: The anticancer effect of hirudin against H22 cells is statistically significant, and its mechanism of action may be related to its modulation of C-met expression.