MicroRNAs (miRNAs) are small non-coding RNAs, which are important in the development of multidrug resistance in cancer by regulating gene expression at the post‑transcriptional level. The present study investigated the functional effects of miR‑522 in chemoresistant colon cancer cells. The results demonstrated that miR‑522 was significantly downregulated in doxorubicin (DOX) resistant colon cell line, HT29/DOX, compared with the parental HT29 colon cancer cell line. Overexpression of miR‑522 in the HT29/DOX cells partially restored DOX sensitivity. miRNA target prediction algorithms suggested that ABCB5 was a target gene for miR‑522. A fluorescent reporter assay confirmed that miR‑522 was able to specifically bind to the predicted site of the ABCB5 mRNA 3'‑untranslated region. When miR‑522 was overexpressed in the HT29/DOX cells, the protein expression levels of ABCB5 were downregulated. Furthermore, knockdown of ABCB5 significantly increased the growth inhibition rate of the HT29/DOX cells, compared with the control group. These results suggested that miR‑522 may affect the sensitivity of colon cancer cell lines to DOX treatment by targeting ABCB5.