Tumor microenvironment responsive drug delivery system presents great potential in tumor-targeted drug delivery. In this study, a poly (ethylene glycol) (PEG) coated biodegradable core-shell microsphere PMAA@DOX-SiO2-PEG with a poly (methylacrylate acid) (PMAA) core and a biodegradable silica layer was prepared. Doxorubicin (DOX) was effectively loaded into the PMAA core and sealed by the silica layer with a drug loading efficiency of 15.3 %. The PEG-modified drug-loaded microspheres present high stability at simulated physiological media with minimized drug leakage (8 %, 56 h), while 80 % drug could be released within 10 h at simulated tumor environment due to the effective carrier degradation. In vitro cell experiments also confirm the good biocompatibility of the blank carrier and the effective tumor inhibition of the drug-loaded microspheres. The study is expected to further promote the development of tumor microenvironment-responsive drug delivery systems.