Cancer stem cells (CSCs) or cancer-initiating cells are a small subpopulation that exhibit a self-renewing capacity and are responsible for tumor heterogeneity, maintenance and metastasis. This hierarchical tumor-initiating concept provides a new hypothesis of tumor formation mechanism. The recent progress in lab researches have demonstrated that CSCs possess the capability of self-renewal, multi-lineage differentiation, and have the ability to generate a new tumor after xenotransplantation of small amount of CSCs in immunocompromised animals. Radiotherapy (RT) has been applied to cancer for more than one hundred years, and treatment responses to RT depend most on the intrinsic radiosensitivity of different types of cancer cells. Some researchers also found that these CSCs were more resistant to chemotherapeutic drugs and ionizing radiation, which play very important roles in conventional cancer therapy. If the radioresistant CSCs cannot be overcome entirely, cancer relapse will be a consequential fate after conventional RT.