Numerous studies demonstrate that the NDV-mediated gene therapy is a promising new approach for treatment of cancer. VEGF-Trap plays a vital role in anti-angiogenesis. Therefore, we hypothesize that a recombinant NDV (rNDV) expressing VEGF-Trap would be an ideal agent for the colon cancer therapy. In this study, VEGF-Trap gene was incorporated into the genome of rNDV (named rNDV-VEGF-Trap). rNDV-VEGF-Trap reduced cell growth ratio by 85.37% and migration ratio by 87.9% in EA.hy926 cells. In vivo studies, treatment with rNDV-VEGF-Trap reduced tumor volume of CT26-bearing mice by more than 3 folds and tumor weight by more than 4 folds. Immunohistochemistry analysis of CD34 showed rNDV-VEGF-Trap significantly decreased the number of vascular endothelial cells in the tumor tissues of the tumor-bearing mice. Moreover, Western blot analysis demonstrated that treatment with rNDV-VEGF-Trap significantly decreased the phosphorylation levels of AKT, ERK1/2 and STAT3 and increased the expression levels of P53, BAX and cleaved caspase-3 in the tumor tissue. In addition, to evaluate the toxicity of VEGF-Trap, serum chemistries were analyzed. The results showed that rNDV-VEGF-Trap caused insignificant changes of creatinine levels, alanine aminotransferase (ALT) and aspartate transaminase (AST). Futhermore, administration of rNDV-VEGF-Trap did not cause the diarrhoea，decreased appetite, weight decrease and haemorrhage of the experimental mice. These data suggest that rNDV-VEGF-Trap exhibits an enhanced inhibition of CT26-bearing mice by enhancing anti-angiogenesis and apoptosis. rNDV-VEGF-Trap is a potential candidate for carcinoma therapy especially for colon cancer.