Objective To investigate the effects of astragalus polysaccharides(APS) combined with 5-fluorouracil (5-FU) on epithelial-mesenchymal transition ( EMT ) in hepatocellular carcinoma HepG2 cells and determine the underlying mechanisms. Methods MTT and Transwell assays were used to investigate the effects of Astragalus polysaccharides and 5-FU alone or in combination on the proliferation and invasion of HepG2 cells, respectively. The expression of EMT-related factors was detected by RT-qPCR and Western blot. Results Astragalus polysaccharides and 5- FU alone or in combination inhibited the proliferation and migration of HepG2 cells. RT-qPCR and Western blot result showed that Astragalus polysaccharides and 5-FU alone or in combination upregulated the expression of E-cadherin and downregulated the levels of vimentin and CXCR4 in HepG2 cells. The greatest effect was observed with 785. 26 μmol / L Astragalus polysaccharide + 23. 90 μmol / L, followed by 392. 63 μmol / L Astragalus polysaccharide + 23. 90 μmol / L 5- FU, 23. 90 μmol / L 5-FU, 392. 63 μmol / L Astragalus polysaccharide, and the blank control. Conclusions Astragalus polysaccharide combined with 5-FU can significantly inhibit the growth and metastasis of hepatoma cells, and the underlying mechanism may be related to inhibition of EMT.