Gold nanoparticles are being actively studied for photothermal therapy (PTT)-based treatment of cancers due to localized surface plasmon resonance (LSPR) effect and excellent photothermal conversion ability. In particular, Gold nanostars has a higher surface area than other gold nanoparticles, and it is highly photothermal efficiency and easy to bio-conjugation. In this study, we investigated the anticancer effect and their cell death mechanism by gold nanostar (GNS) conjugated with hyaluronic acid (HA) targeting CD44 receptor that is overexpressed in breast cancer. The characterization of GNS was confirmed by TEM, UV-visible Spectroscopy. Cell uptake test of GNS was confirmed by ICP-MS. In the cell viability test, photothermal therapy with HA-GNS showed specific cell death in breast cancer cell compared with normal cells. Flow cytometry and western blot analysis revealed that HA-GNS induced apoptosis and necroptosis in breast cancer cells. And proteomic experiments were carried out to elucidate the mechanism of necroptosis. Necroptosis is known to be a programed cell death process that induces the activation of immune cells by causing an inflammatory reaction in the tumor microenvironment. Therefore, HA-GNS photothermal therapy is proposed to induce not only the death of cancer cells but also the activation of immune cells in tumor microenvironment.