While the progress of chemotherapy and molecular targeted therapy has improved the outcome of colorectal cancer patients, the mortality of colon cancer remains high, indicating the need to develop novel therapeutic targets for improving the outcome of colon cancer. Heterogeneous ribonucleoprotein A1 (hnRNP A1) is highly expressed in colorectal cancer and its expression correlates with malignant transformation. In this study, we performed a microarray analysis with the RNA immunoprecipitation (RNA-IP) method and identified hnRNP A1-interacting miRs, including miR-26a and -584, in a colorectal cancer cell line, SW620. A SRB assay revealed the tumor suppressive effect of miR-26a and -584, and the tumor suppressive effect of these miRs was diminished by the downregulation of hnRNP A1. The combined method of a transcriptome analysis and RNA-IP revealed hnRNP A1-interacting mRNAs, including cyclin dependent kinase 6 (CDK6). A Western blot analysis revealed the downregulation of CDK6 in miR-26a and -584 overexpression cells, as well as hnRNP A1 knockdown cells. The binding assay indicated that the binding of hnRNP A1-CDK6 mRNA was reduced by transfection of miR-26a and -584. The expression of cleaved caspase-3 was induced in miR-26a and -584 overexpression cells. These data indicate that miR-26a and -584 inhibit the binding of hnRNP A1-CDK6 mRNA and induce colorectal cancer cell apoptosis. (C) 2015 Elsevier Inc. All rights reserved.