The results of our study indicate that poziotinib increases the efficacy of chemotherapeutic drugs (i.e., reverses MDR) in MDR colon cancer cells by interacting with and affecting the efflux activity of the ABCG2 and ABCB1 transporters and the protein expression level of the ABCG2 transporter. Here, ABCG2 is linked to colonic neoplasm.