Abstract: Objective To investigate the effects of aspirin on the growth and proliferation of human colon cancer cell lines HT-29 and SW480, and the protein and mRNA expression of vascular endothelial growth factor(VEGF) and β-catenin in those cell lines, in order to provide the experimental and theoretical basis for clinical prevention and treatment of colon cancer. Methods We applied aspirin on cultured human colon cancer cell lines HT-29 and SW480, MTT colorimetric assay was used to detect the growth and proliferation of HT-29 and SW480 cell lines. Real-time PCR and Western blot were applied to detect the mRNA and protein expression of VEGF and β-catenin. Results Aspirin had significant inhibitory effects on the growth and proliferation of HT-29 and SW480 cell lines in a dose- and time- dependent manner. Compared with the control group, except 6h intervention group, the mRNA and protein expression of VEGF and β-catenin in other intervention groups were significantly reduced in cultured HT-29 and SW480 cell lines (P<0.05). Conclusion Aspirin has significant inhibitory effects on the growth and proliferation of human colon cancer cell lines HT-29 and SW480, and could reduce the expression of VEGF and β-catenin mRNA and protein. Aspirin inhibiting the expression of β-catenin and VEGF, thereby inhibiting the angiogenesis may be one of the prevention and treatment mechanism of colon cancer.