Abstract: Objective To detect the expression of miR-124 in colorectal carcinoma (CRC) cells and tissue specimens and analyze its association with the radiosensitivity of the cells. Methods The expression of miR-124 in CRC cell lines and tissues were detected using qRT-PCR. The effect of miR-124 in modulating cell radiosensitivity was assessed in CRC cells with miRNA-124 overexpression and miRNA-124 knockdown, and bioinformatics prediction and dual luciferase reporter system were employed to identify the direct target of miR-124. Results miR-124 expression was down-regulated in CRC cell lines and tissues. CRC cells over-expressing miR-124 showed an obviously enhanced radiosensitivity, whereas miR-124 knockdown resulted in a reduced radiosensitivity of the cells. Bioinformatics prediction and dual luciferase reporter system verified PRRX1 as a direct target of miR-124, which regulated the radiosensitivity of CRC cells by directly inhibiting PRRX1. Conclusion miR-124 can enhance the radiosensitivity of CRC cells by directly targeting PRRX1, which provides a target for improving the therapeutic effect of radiotherapy of CRC.