Upregulation of LCN2 effectively suppressed CRC cell metastasis both in vitro and in vivo. TGFB1 and CXCL5 were identified as downstream target genes of LCN2, and rescue experiments verified the necessity of TGFB1 and CXCL5 in LCN2-mediated CRC cell migration and invasion. Here, LCN2 is linked to colorectal carcinoma.