Inventing a tumor-responsive theranostic nanoconstruct shows great potential for improving the therapeutic outcome on cancer. Herein, a facile in situ growth strategy based on polyoxometalate (POM) integrated with the mesoporous silica coated upconversion nanoparticles (UCNPs@mSiO) has been developed. The product was named as USP, and can be triggered by 808 nm light for cancer theranostic. The POM is ultra-sensitive to the intratumoral acidity and reducibility, which enables the photothermal conversion of 808 nm photon for photothermal therapy (PTT). The POM endows the nanostructure highly hydrophilic surface, which is very significant for in vivo application. Need to point out, the photothermal conversion ability of POM enhances the inner temperature of doxorubicin (DOX)-loaded USP (USP-DOX), realizing a bioresponsiveness and NIR photon co-enhanced chemo-photothermal therapy. The POM can also obviate the DOX leakage in normal tissues while accelerate DOX release in tumor tissues under NIR irradiation. Significantly, the POM endows the nanomedicine self-assemble property in acidic tumor microenvironment, which is highly beneficial for enhancing intratumoral accumulation. Highly effective anticancer therapy of the developed USP-DOX has been validated by the in vitro and in vivo assays. The Gd/Nd/Yb/Er co-doped UCNPs ensure the nanosystem MRI/CT/UCL imaging functions, thus achieving the integration of therapy and diagnosis.