Aurora A kinase plays a vital role in mitosis, which is highly expressed in various human cancer cells. Securin has shown to regulate mitosis and prevents abnormal chromosomal segregation that is also highly expressed in several tumor cells. However, the co-regulation of Aurora A and securin in the mitotic progression of human cancer cells remains unclear. Here we show that Aurora A and securin can co-regulate the mitotic progression in the human colon cancer cells. Aurora A proteins could bind to securin proteins in colon cancer cells by using immunoprecipitation assays. Interestingly, the securin-null colon cancer cells markedly reduced the protein levels of phosphorylated and total Aurora A. Moreover, transfection with a GFP-securin-expressed vector increased the Aurora A protein levels. The knockdown of Aurora A by transfection with an Aurora A shRNA vector reduced the securin protein expression. In contrast, transfection of a GFP-Aurora A-expressed vector increased the securin protein levels. The loss of Aurora A and securin induced the abnormal chromosome segregation, mitotic arrest and growth inhibition. Besides, Nocodazole, a mitotic inhibitor, induced mitotic arrest and the abnormal expression and location of Aurora A proteins in colon cancer cells. Taken together, these findings demonstrate that Aurora A and securin may co-regulate the mitotic progression in human colon cancer cells.