Nanozymes, as a new generation of artificial enzymes, offer great opportunities in biomedical engineering and disease treatment. Synergizing the multiple intrinsic functions of nanozymes can improve their performance in biological systems. Here, we report a novel nanozyme with yolk–shell structure fabricated by combining a single gold nanoparticle core with a porous hollow carbon shell nanospheres (Au@HCNs). Au@HCNs exhibited enzyme-like activities similar to horseradish peroxidase and oxidase under an acidic environment, showing the ability of ROS generation. More importantly, the ROS production of Au@HCNs was significantly improved upon 808 nm light irradiation by the photothermal effect, which is often used for tumor therapy. Cellular and animal studies further demonstrated that the efficient tumor destruction was achieved through the combination of light-enhanced ROS and photothermal therapy. These results implied that the intrinsic enzyme-like activity and photothermal conversion of nanozymes can be synergized for efficient tumor treatment, providing a proof-of-concept of tumor catalytic–photothermal therapy based on nanozymes.