The mechanism for the chemoresistance of cancer cells is quite complicated. Most of the anti-cancer drugs are known to induce apoptosis in cancer cells, as well as in normal cells, in part by the activation of the p53 pathway. p53 is often referred to as the 'guardian of the genome' and is one of the most investigated tumor suppressor genes. A majority of human tumors harbor p53 mutations which can influence the effect of chemotherapy. Thus pre-therapeutic evaluation of the p53 gene can be extremely informative for patients with diverse malignancies. In this mini review, we introduce a p53 functional analysis system in mammalian cells, which can identify different types of p53 abnormalities, such as loss of function, dominant negative function, or gain of oncogenic function. The kinetic analysis of mutated-p53 may help to determine the therapeutic strategy in the individual patients with several malignancies. Furthermore, detailed information on the mutated p53 gene in cancer cells might provide useful suggestions for developing new anti-cancer drugs.