Resulting from their versatile functionality, nanomaterials with low systemic toxicity have offered high-performance diagnostic and therapeutic capabilities. Here, we designed and synthesized uniform magnesium silicate hollow spheres as high drug-loading nanocarriers for cancer therapy. Through a classical Stöber method and a hydrothermal process, well-defined MgSiO3 hollow spheres were prepared in a facile route with inexpensive inhesion. Compared with routinely used mesoporous silica nanoparticles, our MgSiO3 hollow spheres with larger void space and mesoporous shell endowed the structures with a much higher storage capacity of guest molecules (2140 mg DOX g(-1)) and a much more sustained release of anticancer drugs. In detail, the release property and therapeutic efficacy of DOX-loaded nanoparticles were evaluated in vitro and in vivo. In vitro experiments revealed that these nanoparticles were mostly accumulated in lysosome, which facilitated continual drug release and efficient cancer cell destruction. We further demonstrated that these DOX-loaded nanoparticles could effectively suppress tumor growth compared to free DOX in vivo, as DOX-loaded-nanoparticle-treated mice survived over 15 days without obvious detectable tumor growth. Otherwise, long-term toxicity study was also evaluated, indicating their overall safety and great potential in biomedical applications.