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Background: In the bystander effect, non-irradiated cells receive biological signals from adjacent irradiated cells and undergo a variety of alterations, considered recently in non-ionizing irradiation like ultrasound waves. This study was conducted to assess this effect on simultaneous administration of ultrasound and gold nanoparticles as a sonodynamic therapy which is an important newly stimuli-responsive method in cancer treatment. Materials and Methods: Firstly, the appropriate concentration of Gold Nanoparticles (GNPs) and ultrasound intensity for sonodynamic therapy on melanoma cancer cells (A375) were evaluated. After treatments, the target cell culture was transferred to the bystander cells and the induced bystander effects including cell viability, apoptosis, expression of P53 (a promoter of apoptosis gene) and HO-1 (an inhibitor of apoptosis gene) were examined. Results: According to the MTT results, 50 µg/ml concentration of GNPs and 1.5 W/cm2 intensity of ultrasound wave were selected. Our results revealed that sonodynamic therapy induced bystander effect can alter the cell viability and apoptosis up to 20% and 51.61%, respectively. Moreover, a 2.9-fold increase in P53 gene expression and a decrease in OH-1 gene expression to 0.181-fold in comparison to the control groups were observed. Conclusion: These results confirmed that bystander effect of sonodynamic can reduce the cancerous cell viability. Our finding showed that this treatment can potentially be an alternative to traditional treatment modalities. [ABSTRACT FROM AUTHOR]