Nowadays, there is growing interest regarding the use of metal Nanoshells as targeted agents of Nano-photo thermal cancer therapy. This study was aimed at synthesis the folic acid (FA)-conjugated with silica @gold core-shell nanoparticles (FA-SiO@AuNPs) for improving the treatment of melanoma cancer cells. The characterization data showed that the FA-SiO@AuNPs is spherical in shape and its size is ∼73.7 nm. The intracellular uptake of FA-SiO@AuNPs into melanoma cells (A375 was measured through the inductively coupled plasma, (∼47.7%). The cytotoxicity of nanoparticles was investigated on A375 and HDF (Human dermal fibroblast) cell lines. Cytotoxicity results indicated that there is no significant cytotoxicity in HDF cell lines treated with nanoparticles. MTT and flow cytometry results showed that the viability of A375 cells treated by SiO@Au and FA-SiO@AuNPs was decreased significantly to about 31% and 16% respectively. The higher toxicity of cancer cells was obtained for the cells exposed to 808 nm near-infrared (NIR) laser after incubation with FA-SiO@AuNPs rather than the non-targeted SiO@AuNPs. Furthermore, about 64% more cell death was observed for A-375 cells using both photothermal therapy and treatment with FA-SiO@AuNPs compared to photothermal therapy. Additionally, the majority of the cell deaths were related to the apoptosis process, not necrosis. It can be concluded that FA-SiO@AuNPs was an effective targeting agent for photothermal therapy in the treatment of melanoma.