Radiotherapy is a commonly used treatment for cancer patients worldwide. However, not all cancer patients respond well to radiation treatment. Studies have provided strong evidence that epigenetic mechanisms may be a major reason for the failure of radiotherapy. The specific epigenetic changes at the molecular level and their effects on the response to radiation treatment are not fully understood. In recent years, it has become clear that these factors, particularly DNA methylation-related genes and associated cellular mechanisms, play a role in individual sensitivity to radiation and can induce radioresistance. The genes controlling the signaling of significant cellular responses upon radiation exposure are key players in this process. A relationship between DNA methylation and the response to radiotherapy has been observed in several types of cancer, including cervical cancer. Epigenetic changes such as DNA methylation and miRNA may affect the repair of DNA damage caused by radiotherapy, leading to a differential response to treatment. Studies have shown that cancer cells with a high level of DNA methylation are more resistant to radiotherapy, whereas those with a low level of DNA methylation are more sensitive. These findings suggest that the status of epigenetic changes may be a predictive marker for the response to radiotherapy. Understanding these underlying mechanisms is essential because they can be targeted with radiosensitizers to improve therapeutic efficacy. Additionally, DNMT inhibitors have been shown to selectively enter and destroy the DNA of tumor cells. This review summarizes recent updates on epigenetic factors that contribute to radiosensitivity and discusses how these insights can be used to maximize the therapeutic benefits of radiotherapy.