Deficient signaling of the EGFR and other receptor tyrosine kinases in humans is associated with diseases such as cancer. Some EGFR tyrosine kinase inhibitors have become a new class of targeted therapeutic agents in the last years. We found that 27-O-p-(E)-coumaroyl ursolic acid (27-CAUA) had a strong activity of apoptosis according to preparation by screening for a series of Ilex latifolia products. 27-CAUA inhibited EGFR kinase system to lead to inactivation of PI3K/AKT/mTOR and Ras-Raf-MEK-ERK signal pathways which implicated in the proliferation and survival of tumor cells. These findings suggested that 27-CAUA was an orally active, selective epidermal growth factor receptor-tyrosine kinase inhibitor which could lead to beneficial manifestations in the clinic.