Metadherin (MTDH) promotes cancer metastasis, chemoresistance, invasion and angiogenesis. Upregulation of MTDH is correlated with both progression and poor clinical outcome of many types of cancers; however, there is currently no information regarding the role of MTDH in radiation sensitivity. Here, we investigated the effects of MTDH on the radiosensitivity of cervical cancer cells using the SiHa cell line. We discovered that cervical cancer cells in which MTDH was knocked down had significantly increased radiosensitivity as measured by a clonogenic assay. MTDH knockdown cells also had increased apoptosis and a decreased proportion of cells arrested in the G2 phase after radiation treatment. MTDH knockdown also weakened the repair of DNA double-strand breaks (DSBs) induced by radiation. These results indicate that MTDH affects the radiosensitivity of cervical cancer cells and that MTDH may be a novel target to improve cervical cancer radiation response.