Near-infrared (NIR) photothermal therapy has developed very quickly in recent years. However, its clinical applications are hindered by many practical problems, such as low accumulation in tumors, high laser power density and high biotoxicity in vivo . Herein, a versatile system combining chemotherapy with photothermal therapy for cancer therapy using ultrasmall Pd nanosheets (SPNS) has been developed. The SPNS can serve as pH-responsive drug carriers to efficiently deliver DOX into cancer cells and tumors. On the other hand, the coordinative loading of DOX on SPNS enhances its accumulation in tumor tissue. So we can efficiently ablate tumor using low-intensity laser radiation. Importantly, with ultrasmall size (~4.4 nm), SPNS surface-functionalized with reduced glutathione (GSH) can be cleared from the body through the renal system into the urine. This cancer therapeutic nanosystem, which exhibits a significant synergistic effect and low systemic toxicity, has great potential for clinical applications.