Gold nanomaterials have attracted great interest in the fight against cancer due to their surface features. In this study, gold nanostar (GNS) cloaked with mesoporous silica (GNS@mSiO2) carriers were prepared for controlled drug release. The GNS core presents a branched morphology with tip-to-tip diameter of 80–120 nm and core of 40–60 nm. In this system, GNS not only served as photothermal agent but also as Raman signal enhancement matrix. After encapsulating doxorubicin (DOX) within the GNS@mSiO2 carrier, hyaluronic acid (HA) was coated on the GNS@mSiO2 surface to seal the loaded-drug of channels. The obtained DOX-GNS@mSiO2/HA displayed pH/enzyme-triggered drug release and photothermalchemo therapeutic effect.