Both photothermal therapy (PTT) and photodynamic therapy (PDT) are phototherapeutic approaches, which have been widely investigated for cancer therapy mediated by near infrared (NIR) light irradiation. Here, we successfully constructed a single-light triggered indocyanine green (ICG)-loaded gold nanocomposites which were composed of gold nanoflower core/two layers silica shell (AuNFs@SiO₂@mSiO₂-ICG) for enhanced PDT/PTT synergistic effect to oral carcinoma. The AuNFs@SiO₂@mSiO₂-ICG nanocomposites had no obviously cytotoxicity and could effectively arrest Cal27 cells in the G1 phase. Moreover, the conjugation of ICG caused significantly higher reactive oxygen species (ROS) productivity and apoptotic Cal27 cells compared to free ICG or free AuNFs@SiO₂@mSiO₂. In this study, compared with PTT or PDT alone, synchronous PTT and PDT produced by AuNFs@SiO₂@mSiO₂-ICG under NIR light irradiation induced enhanced Cal27 cells lethality in vitro and tumor growth inhibition in vivo, which might be a promising strategy for cancer treatment.