In conclusion, the present study demonstrated that in CD44+/CD133+ CSC-like cells, miR-139-5p could reverse MDR by downregulating NOTCH1. These findings suggest the potential feasibility of miR-139-5p as a biomarker and novel anti-cancer drug target, and provide a full-scale theoretical basis and new strategy for CRC diagnosis, targeted therapy and prognosis. This evidence concerns the gene CD44 and cancer.