The past decades have witnessed great achievements in the synergistic therapy for tumors, especially chemo-photothermal synergistic therapy. However, due to the high working temperatures (>50 °C) of photothermal therapy, the peripheral tissue nearby tumors usually get burned, which limits the further clinical application of chemo-photothermal synergistic therapy. Thus, a mild chemo-photothermal synergistic therapy for tumor is eagerly awaited. Herein, a chemo-photothermal synergistic tumor therapy working under mild temperatures (43 °C) based on gold nanoparticles coupled with metformin was developed. In the 4T1-tumor bearing mice model, the tumor inhibition rate reached 94.6%. The interaction coefficient of this nano-conjugates was 0.2, indicating a high synergistic effect between chemoand photothermal therapy for tumors. Furthermore, pathological tests showed that the nanoconjugates prevent the tumor metastasis to the lung. Together with good targeting ability of tumor microenvironments and good biocompatibility, this work provides a potential drug candidate for the mild chemo-photothermal synergistic therapy for tumors.