Tumor suppressor protein p53 is a transcription factor that plays important roles in biological responses to a wide range of ionizing radiation doses. Elucidation of the molecular mechanisms for its function after actually relevant doses of radiation is therefore crucial for the accurate understanding of the biological effects of radiation. p21 is one of the p53 target genes, functioning in cell cycle checkpoint regulation. In this article, a comprehensive analysis of the p21 gene promoter after clinically relevant doses of radiation is reviewed, especially emphasizing that a transcription factor Oct-1 plays a cooperative role in p53-mediated regulation of the p21 gene after irradiation. In addition, a potential application of the p21 gene promoter in the development of a low-dose radiation inducible vector for cancer gene therapy is also pointed out.