Nanoparticles-based drug delivery system for synergetic chemo-photothermal therapy is an efficient strategy for tumor therapy. However, construction of nanodrugs with high drug loading capacity and good photothermal conversion property is still a great challenge. In this work, two-dimensional boron nanosheets were prepared by ultrasonic liquid exfoliation method, which were further loaded with ultra-small copper sulfide (CuS) nanoparticles and doxorubicin (DOX) to obtain B-CuS-DOX nanocomposites. The prepared B-CuS-DOX exhibited high drug loading capacity (864 mg/g) and excellent photothermal conversion efficiency (55.8%). In addition, B-CuS-DOX exhibited pH and laser--responsive drug release behavior. In vitro results demonstrated that the prepared B-CuS-DOX achieved a good synergistic effect of chemotherapy and photothermal therapy. This work is expected to provide an effective chemo-photothermal synergistic therapy strategy for tumor therapy.