Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant tumor worldwide. Considering its special anatomical site and the progressive resistance to chemotherapy drugs, the development of more effective, minimally invasive and precise treatment methods is urgently needed. Nanomaterials, given their special properties, can be used as drug carrier systems to improve the therapeutic effect and reduce the adverse effects. The drug carrier systems with photothermal effect can promote the killing of cancer cells and help overcome drug resistance through heat stress. We selected dopamine, a simple raw material, and designed and synthesized three different configurations of nano-polydopamine (nPDA) nanomaterials, including nPDA balls, nPDA plates and porous nPDA balls. In addition to the self-polymerization and self-assembly, nPDA has high photothermal conversion efficiency and can be easily modified. Moreover, we loaded cisplatin into three different configurations of nPDA, creating nPDA-cis (the nano-drug carrier system with cisplatin), and comparatively studied the properties and antitumor effects of all the nPDA and nPDA-cis materials in vitro and nPDA-cis in vivo. We found that the photothermal effect of the nPDA-cis balls drug carrier system had synergistic effect with cisplatin, resulting in excellent antitumor effect and good clinical application prospects. The comparison of the three different configurations of drug carrier systems suggested the importance of optimizing the spatial configuration design and examining the physical and chemical properties in the future development of nano-drug carrier systems. In this study, we also noted the duality and complexity of the influences of heat stress on tumors in vitro and in vivo. The specific mechanisms and the synergy with chemotherapy and immunotherapy will be an important research direction in the future.© The Author(s) 2024. Published by Oxford University Press.