Abstract: The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT116 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg·kg^-1 inhibited tumor growth by 73.24%. The IC₅₀ of ZLJ213 on the expression of p-Aurora A was 0.258 μmol·L^-1 analyzed by ELISA. Under the concentration of 0.08 μmol·L^-1, ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.