Development of novel strategies is required for cancer treatment because most human tumors are refractory to current conventional therapy. During the past decade, a number of oncogenes and tumor suppressor genes have been cloned and the molecular mechanisms as to how mutations in such genes contribute to tumor development are going to be clarified. It is, therefore, a great challenge to develop novel strategies for tumor specific therapy based on molecular biology of cancer. p53 tumor suppressor gene is one of the most frequently mutated genes in a variety of human cancers. This review paper introduces several recent approaches related to the p53 as a molecular target of cancer treatment, including (i) p53 status and chemo-radiosensitivity, (ii) p53 gene therapy, (iii) E1B-deficient adenovirus and (iv) restoration of p53 function by synthetic polypeptides.