Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is a promising method of tumor treatment, which has the advantages of strong specificity and small side effects. However, PDT will aggravate the hypoxic environment in tumor cells, and PTT will lead to heat-resistant reaction, both of which will make the organism quickly produce heat shock proteins (HSPs) to protect itself, thus seriously hindering the therapeutic efficiency of phototherapy. As a natural HSPs inhibitor, quercetin (QR) provides a feasible way to solve this problem. Herein, a kind of metal organic framework (MOF), Fe-TCPP (FT), was used as a delivery material and photosensitizer to build a chemo-phototherapy platform, and QR was used as a chemotherapy drug and HSPs inhibitor. On this basis, the nanoparticles (NPs) were modified with PEG-CPP30 (a cell-penetrating peptide that specifically recognizes human breast cancer MCF-7 cells), which showed excellent targeting capacity and biocompatibility. The combination of chemotherapy and phototherapy significantly improved the anti-cancer effect. At the same time, NPs also showed prominent anti-HSPs effect. The effective connection of the two played a complementary role in the process of tumor treatment, which provided a new strategy for the accurate and efficient treatment of tumors in the future.