Gold nanomaterials are widely used in biomedical research as drug delivery systems, imaging agents and therapeutic materials owing to their unique physicochemical properties and high biocompatibility. In this study, we prepared ultra-small gold nanoparticles (AuNPs) and induced them with gadolinium ions to form a spherical self-assembly. The nanoparticles were coupled with matrix metalloproteinase-2 (MMP-2) and loaded with the photosensitive drug IR820 for photothermal/photodynamic combination therapy of liver cancer. The formed nanoprobes were metabolised in vivo via degradation under dual-mode real-time imaging because of their acid response degradation characteristics. In addition, the nanoprobe showed excellent tumour-targeting ability due to the presence of surface-modified MMP-2. In vivo treatment experiments revealed that the nanoprobes achieved enhanced photodynamic/photothermal combination therapy under laser irradiation and significantly inhibited tumour growth. Therefore, the nanoprobes have great potential for anti-tumour therapy guided by dual-mode real-time imaging of liver cancer.