Chemically exfoliated two-dimensional MnO2 nanosheets are successfully modified with amino-polyethylene glycol as a theranostic platform for ultrasensitive stimuli-responsive theranostics of cancer. The highly dispersed MnO2 nanosheets exhibit a unique break-up in the mildly acidic microenvironment of tumor tissues, which could substantially enhance their in vitro and in vivo performances in T-1-weighted magnetic resonance imaging. Such a pH-triggered breaking-up behavior could further promote the fast release of loaded anticancer drugs for concurrent pH-responsive drug release and circumvent the multidrug resistance of cancer cells.