The use of nanoparticles as a sonosensitizer in cancer sonodynamic therapy has been gaining attention because of their great advantages in drug delivery applications. By conjugating chemotherapy agents with nanoparticles, we can develop a drug delivery platform, control drug release and improve the outcome of treatments. The in-vitro study described here evaluates the combination of AuSiO2 nanoparticles and dacarbazine ([email protected]2) as a sonosensitizer for sonodynamic therapy of melanoma. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays revealed that the viability of B16F10 melanoma cells was significantly inhibited by the increase in apoptosis induction in treatment with [email protected]2 nanoparticles under ultrasound exposure compared with treatment with the free DTIC or AuSiO2 nanoparticles. The sonosensitization activity of AuSiO2 nanoparticles and greater uptake of DTIC by tumor cells after loading in [email protected]2 nanoparticles inhibited the proliferation of melanoma tumor cells effectively. In conclusion, the [email protected]2 nanoparticles established in this study could represent a good drug delivery and sonosensitizer platform for use in melanoma sonodynamic therapy.