Herein, a pH stimuli-responsive vehicle for intracellular drug delivery using CeO2 capped mesoporous silica nanoparticles (MSN) is reported. β-Cyclodextrin-modified CeO2 nanoparticles could cap onto ferrocene-functionalized mesoporous silica through host–guest interactions. After internalization into A549 cells by a lysosomal pathway, the ferrocenyl moieties are oxidized to ferrocenium ions by CeO2 lids, which could trigger the uncapping of the CeO2 and cause the drugs release. Because of the pH-dependent toxicity, the CeO2 here behaves as a multi-purpose entity that not only acts as a lid but also exhibits a synergistic antitumor effect on cancer cells. Meanwhile, the cell protective effect of CeO2 nanoparticles alone is demonstrated, which ensures that the dissolved CeO2 nanoparticles can be non-toxic to normal cells.