〔Abstract〕 Objective To investigate the effect and mechanism of colchicine on mouse liver cancerviaHippo signaling pathway. Methods The 6-week-old male C57BL/6J mice were randomly divided into 3 groups: diethylnitrosamine(DEN)/carbon tetrachloride(CCl4)/ethanol(C2H5OH) induced mouse liver cancer model and colchicine(0.1 mg/kg) intervention were established in control group, model group and colchicine group. From week 1st to week 2nd, the model group and the colchicine group were intraperitoneally injected with 1.0% DEN once a week. From week 3rd to week 7th, 20% CCl4dissolved in olive oil solution(5 ml/kg) was intragastric administration twice a week. From week 8th to week 18th, 20% CCl4dissolved in olive oil solution(6 ml/kg) was intragastric twice a week. The colchicine group was given continuous intragastric administration for 20 weeks. The control group was given the corresponding solvent. Liver index, alanine aminotransferase(ALT) and aspartate aminotransferase(AST) serum biochemical indexes were detected. Western blot and immunofluorescence were used to detect the expression levels of MST1, pYAP, YAP, pTAZ and TAZ proteins in liver tissues of mice in each group. Results The liver surface of mice in the control group was smooth and soft, while the liver of mice in the model group was rough and hard with granular nodules. The above lesions were significantly improved in the colchicine group. HE staining showed that the liver lobular structure of mice in the control group was normal, while the liver lobular structure of mice in the model group was disordered, with a small amount of fat droplets, extensive tissue necrosis, inflammatory cell infiltration, and fat vacuoles. The degree of liver lesions of mice after colchicine intervention was significantly reduced. The results of immunofluorescence and Western blot showed that compared with the control group, the protein expression levels of pYAP and pTAZ in liver tissue of model group mice were significantly decreased, while the protein expression levels of MST1, YAP and TAZ increased. After colchicine intervention, the protein expression levels of MST1, pYAP and pTAZ were significantly up-regulated, while the protein expression levels of YAP and TAZ were down-regulated. Conclusion The therapeutic effect of colchicine on mouse liver cancer may be related to its activated Hippo signaling pathway.