The effect and primary mechanism of multidrug resistance reverse of cancer cell to Doxorubicin by ganoderic acid Me(GA-Me) was studied.The results showed that GA-Me possessed the cytotoxicity and induced the apoptosis of multidrug resistant cancer cells and sensitive cancer cells under high concentration dose- dependently.The cytotoxicity of doxorubicin on multidrug resistant cancer cells increased by 5μg /mL of GA- Me treatment,this result indicated that GA-Me could reverse the multidrug resistance of cancer cells to doxorubicin.Moreover,the content of doxorubicin and Rhodamin123 in multidrug resistance cancer cells increased 100% respectively by GA-Me treatment.This result indicated that GA- Me might be influence the activity of membrane protein P-gp.The results mentioned above showed that GA- Me could reverse the multidrug resistance of cancer cells to doxorubicin by influence of membrane protein P- gp and induction of apoptosis.The results in this paper provided the theoretical foundation for development of functional food and leading compounds for cancer therapy.