Photothermal therapy (PTT) is a potentially effective and non-invasive tumor therapy that has attracted the attention of many researchers. This study systematically investigated the formation of metal-polyphenol nanoparticles and their photothermal properties. A simple physical self-assembly method was used to embed hyaluronic acid (HA) into metal-polyphenol nanoparticles, and a novel type of HA-modified ferrous baicalein nanoparticle (HFBNP) was successfully prepared for the first time. Unlike most current methods that utilize positive and negative charge attraction or chemical bonding, the method proposed in this study is to embed HA into nanostructures to reduce the risk of HA shedding in the circulation, thereby improving the tumor targeting efficiency while avoiding the use of other chemical reagents. HFBNP had a suitable size distribution and good biosafety meanwhile efficiently converting near-infrared (NIR) laser energy into thermal energy. The active targeting capability mediated by HA significantly increased the uptake of nanoparticles by tumor cells, and HFBNP exhibited a strong growth inhibitory effect on tumor cells under NIR laser irradiation. With the combination of PTT and chemotherapy, HFBNP significantly inhibited tumor growth in tumor-bearing mice. In conclusion, the nanosystem prepared in this study provides a new strategy for tumor therapy.