Abstract: With the increasingly deepening research on the molecular regulatory mechanisms during the development and progres-sion of advanced renal cell carcinoma, the targeted therapy directed on the key proteinase/protein in the molecular signaling pathways significantly improves the management outcomes. However, the occurring resistance during therapy with targeted agents leads to de -creasing effects. The mechanisms of action, resistance, and countermeasures of targeted therapy in advanced renal cell carcinoma are simply reviewed.