〔Abstract〕 Objective Yin Yang Gong Ji Pill is an ancient formula in Ming Dynasty, used to treat the mass and accumulation syndrome with warming Yang, resolving phlegm, and dispersing accumulation. This study explores the effects of the reducing presicription New Gong Ji Pill on tumor angiogenesis and related proteins in liver cancer cell lines in vitro. Methods The drug-containing serum of New Gong Ji Pill was prepared and the inhibition rate of HepG2SG by the drug-containing serum was detected by cell counting kit (CCK)8. Protein expressions of tumor angiogenesis related proteins such as VE-cadherin, Vimentin, transforming growth factor β2 (TGFβ2), Twist1 and CD44 were detected by Western blot. Cell scratch assay and Transwell assay were used to detect the migration and invasion ability of HepG2SG cells. Human umbilical vein endothelial cells (HUVEC) cultured with HepG2SG conditional medium and HepG2SG cells were used to detect angiogenesis in vitro, respectively. Results The proliferation of HepG2SG cells was inhibited by the drug-containing serum in a concentration-dependent way. Compared with the control group and the blank serum group, the inhibitory rates of all concentrations in the drug-containing serum group were significantly increased (P < 0.01). Compared with the control group and blank serum group, the protein expressions of VE-cadherin, Vimentin, TGFβ2, Twist1 and CD44 in New Gong Ji pill containing serum group were down-regulated, and the differences were statistically significant (P < 0.01). The migration and invasion ability of HepG2SG, angiogenesis of HUVEC and angiogenesis mimicry of HepG2SG in drug-containing serum group were significantly reduced compared with the control group and blank serum group (P < 0.001). Conclusion The containing serum of New Gong Ji Pill, which mainly contains drugs of expelling phlegm and eliminating accumulation, can inhibit HepG2SG cells, reduce tumor migration and invasion ability, significantly down-regulate the expression of tumor angiogenesis related proteins, and thus inhibit tumor angiogenesis and angiogenesis mimicry.