Drug release simultaneously with carrier decomposition has been demonstrated in SiO2-drug composite nanoparticles. By creating a radial drug concentration gradient in the nanoparticle, controllable release of the drug is primarily driven by diffusion. Escape of the drug molecules then triggers the SiO2 carrier decomposition, which starts from the center of the nanoparticle and eventually leads to its complete fragmentation. The small size of the final carrier fragments enables their easy excretion via renal systems. Together with the known biocompatibility of SiO2, the feature of controllable drug release and simultaneous carrier decomposition achieved in the SiO2-drug nanoparticles make it ideal for a wide range of diagnostic and therapeutic applications with great promise for potential clinical translation.