Combined therapy with multimodal therapeutic agents based on nanomaterials has been shown as a promising approach to cancer treatment. In this report, a highly efficient multifunctional anti-cancer nanocomposite was fabricated by assembling a photothermal agent (CuS nanoparticles) and a photodynamic agent (g-CN quantum dots) on upconversion nanoparticles (UCNPs) after mesoporous silica coating. Then, the surface modification of the obtained nanocomposite (abbreviated as CUSCs) with polyethylene glycol (PEG) and folic acid (FA) endows the final sample (denoted as CUSCs-PEG-FA) with an excellent cancer cell targeting effect and biocompatibility. In this nanoplatform, CuS nanoparticles are an inorganic substance with low toxicity and high photothermal conversion efficiency. g-CN QDs have excellent biocompatibility and are beneficial for cellular uptake due to their small size. UCNPs can be excited by near-infrared (NIR) light to produce ultraviolet and visible (UV–vis) light emission, which overlaps with the UV absorption peak of high fluorescence g-CN quantum dots (QDs). Therefore, when the nanocomposite is excited by 808 nm NIR light, a synergistic treatment effect will be presented. Since the wavelengths absorbed by the chosen photothermal agent and the photosensitizer are different, sufficient utilization of energy can be achieved. Combining photothermal therapy (high photothermal conversion efficiency of 27.4%) and photodynamic therapy can inhibit cancer more effectively compared to any monotherapy. Moreover, as a result of the inherent performance ability of the doped rare earth ions, excellent applicability for computed tomography (CT), upconversion luminescence (UCL) and magnetic resonance imaging (MRI) has been achieved.