Abstract: OBJECTIVE To clarify that Yupingfeng San (YPFS) can inhibit the formation of microvessels by inhibiting the activation of thymic stromal lymphopoietin (TSLP) and signal transduction factor (STAT3)， and exert its anti-liver effect. METHODS Hepa1-6 orthotopic liver cancer mouse model was used， and YPFS solution (20， 30， 40 g/kg) was intragastrically administered. The mice were sacrificed two weeks after administration. The tumors were weighed and the tumor inhibitory rate was calculated. The expression levels of VEGF， TSLP and TSLPR in tumor tissues and adjacent tissues were detected by ELISA. The expression of MVD in microvessel density was detected by immunohistochemistry. The protein expression of STAT3 and p-STAT3 was detected by Western blot. RESULTS Compared with the model group， different concentrations of YPFS (20， 30 and 40 g/kg) groups significantly inhibited tumor growth in a dose-dependent manner (P<0.05， P<0.01)， the tumor inhibitory rate was 26.37%， 35.89% and 56.01%， respectively; the MVD and VEGF levels of tumor tissues and adjacent tissues in YPFS groups were significantly reduced (P<0.05， P<0.01); further studies showed that the expression of TSLP/TSLPR and p-STAT3/STAT3 in YPFS-treated groups could be reduced in dose-dependent manner(P<0.05， P<0.01). CONCLUSION YPFS attenuates the activation of TSLP-STAT3 signaling pathway by inhibiting the expression of TSLP， thereby inhibits the formation of blood vessels in the hepatic microenvironment and exerts anti-HCC effect. The study provideds experimental basis for new strategies for prolonging the survival of liver cancer patients and developing ideal therapeutic drugs targets.