We constructed triple-stimuli-responsive nanocontainers (T-SRNs), consisting of mesoporous silica nanoparticles for accommodating cargoes and bistable [2]pseudorotaxanes for regulating cargoes and realizing controlled release. T-SRNs eliminate premature leakage of model cargoes under neutral solution conditions by the formation of complexes of water-soluble carboxylate-substituted pillar[5]arenes (WP5) with 1,6-hexanediammonium (HDA) recognition stations to block pore orifices. After exposure to acid, alkali pH or Zn2+ environments, T-SRNs release encapsulated cargoes promptly, which can be attributed to the dethreading of WP5 from HDA sites by different approaches and the lack of stoppers. The unique acid/alkali/Zn2+-responsive controlled release characteristic mean that T-SRNs have potential in some application fields. Herein, MTT assays and in vitro release of doxorubicin from T-SRNs demonstrate that T-SRNs can serve as promising targeted drug delivery vehicles.