MicroRNAs (miRNAs) represent an important nonprotein part of the human genome in tumor biology. Among the several types of miRNAs, microRNA-21 (miR-21) is dysregulated in several types of cancer and plays a key role in carcinogenesis, recurrence, and metastasis. Thus, it can be a potential target for cancer therapy including radiation therapy. In this review, we focus on miR-21, which has been identified in human cancer tissues, to suggest reasonable strategies for future research. miR-21 may have an influence on cell cycle, DNA damage repair, apoptosis, autophagy, and hypoxia of cancer during irradiation. We review the use of miR-21 in cancer radiation therapy and describe the known functions and possible underlying molecular mechanisms of miR-21 in radiosensitivity and radioresistance. Furthermore, the current and potential future applications of miR-21 in cancer radiation therapy are also discussed.