Our findings identify that anlotinib exhibited a strong effect on anti-angiogenesis, anti-metastasis, anti-proliferative and anti-multidrug resistance in CRC by blocking the EGFR, MET, and ABCB1 signaling pathways, which exhibited a robust pharmacological effect in the CRC liver metastases xenograft model. Here, EGFR is linked to colorectal carcinoma.