The expression of circ-NSD2 in liver metastases of a mouse model is higher than that in its paired primary colon tumors and non-cancerous organs. The overexpression of circ-NSD2 enhances migration and invasion of HCT116 in vitro. Silencing of circ-NSD2 reduces migration and invasion of HCT116 and RKO cells in vitro. Circ-NSD2 may up-regulate DDR1, JAG1, and their downstream signals by targeting miR-199b-5p to inhibit the growth and metastasis of CRC. Here, NSD2 is linked to colonic neoplasm.