Chemoresistance is still one of the main obstacles to treat colorectal cancer (CRC). Substantial studies on biomarkers related to chemoresistance have emerged in recent years. Many microRNAs (miRNA) have been reported to involved in drug resistance and CRC. MiR-126-5p participates in malignant behaviors of numerous cancers. However, it is not known if miR-126-5p participates in multidrug resistance in CRC. Especially, the impact of miR-126-5p on drug resistance of CRC and its drug resistance mechanism have not been reported.