Allelic loss and mutation of the p53 gene are common events of esophageal, gastric and colorectal cancers occurring from an early stage. Moreover, p53 mutation takes place in intestinal metaplasia and adenoma of the stomach. p53 mutation spectra differ among esophageal, gastric and colorectal cancers suggesting exposure to different endogenous and exogenous mutagens. The in vivo and in vitro results indicate that the clonal expansion of p53 mutant cell may be associated with tumor progression. Although wild type p53 transfection technique may provide for cancer therapy, there is a rather serious problem about it.