Abstract: The roles of P53 protein in the inhibitory effect of ganoderic acid T ( GA- T) on human lung cancer cells proliferation were evaluated by H1299 ( p53- /-) and 95-D ( p53+ / +) cells.The results showed that 95-D cell which expressed P53 protein was more sensitive to the GA- T than H1299 cell which unexpressed P53 protein. The cytotoxicity of GA- T on 95- D cells was 3.3 times higher than that of H1299 cell significantly. The cytotoxicity of GA- T on 95- D cancer cells decreased significantly after pifithrin- α treatment ( p < 0.05) . Furthermore, GA- T stimulated the expression of P53 in 95- D cancer cells and induced the apoptosis of 95- D cancer cells dose-dependently.The results mentioned above proved that P53 participated in the process of anti- proliferation of cancer cell by GA- T and should be a potent target of ganoderic acids.The results in this paper should provide the theoretical foundation for development of functional food.