Given the consequent results that miR-125b-5p was apparently negatively associated with cisplatin resistance in colon cancer, both our in vitro and in vivo data consistently elucidated a DANCR–miR-125b-5p/HK2 axis in the acquired cisplatin resistance, suggesting targeting this molecular pathway contributes to develop therapeutic approaches against chemoresistance of colon cancer. This evidence concerns the gene HK2 and malignant colon neoplasm.