An efficient theranostic nanoplatform responding to tumour microenvironments with characters of simple and flexible combinations owns great potential in cancer diagnosis and therapy. Herein, a series of triblock copolymers, mPEG-b-PDPA-b-P(nBMA-r-cystamine) (EPB), were synthesized and among them, the structure of EPB-3 was optimized for both fluorescence imaging-guided cancer diagnosis and multi-modal therapy with good biocompatibility. (1) The self-assembled nanoparticles of EPB-3-ICG1 obtained by conjugating one ICG on EPB-3 via S-S bonds effectively performed reduction-sensitive OFF/ON fluorescence signal transition, thus inducing tumour cell-specific amplified fluorescence imaging in vitro and in vivo. (2) By entrapping Au nanorods into the co-assembled NPs of EPB-3 and EPB-3-ICG1, EPB-3-ICG1@Au NPs could synchronously induce strong tumour fluorescence imaging and high local photothermal effect, indicating the potential of imagine-guided photothermal therapy. (3) EPB-3 NPs could efficiently co-load paclitaxel (PTX) and ICG to form stable EPB-3@PTX@ICG NPs, which provided long periods of intracellular pH-sensitive sustainable drug release and highly enhanced apoptosis of 4T1 cells in vitro by the chemo-photothermal effect. Excitingly, a single intravenous injection of EPB-3@PTX@ICG NPs followed by a one-time local near-infrared light (NIR, 808 nm) irradiation treatment for 10 min could lead to significant inhibition of tumour growth, avoiding tumor metastasis and extending the survival of mice. All the above-mentioned results suggest that EPB-3 provides a nanoplatform with the characters of simple structure, convenience of use and flexible combination, holding potential for multi-modal diagnosis and therapy.