Radiotherapy is a standard treatment for many cancers and is frequently used as primary or adjuvant therapy, often in combination with surgery or chemotherapy or both. However, locoregional recurrence or metastatic spread still occurs in a high proportion of patients after radiotherapy. In this regard, emerging evidences suggest that sublethal radiation paradoxically promotes expansion of cancer stem cell population that is highly tumorigenic and is reminiscent of non-neoplasm stem cells. In this review, we discussed recent findings that demonstrate the increase in cancer stem cells after irradiation, and the possible cellular mechanisms with a perspective of tumor microenvironment. A further understating on the mechanistic mechanisms underlying radiation-enhanced malignant phenotypes might increase the efficacy of radiotherapy for cancer treatment.