Three main parameters affecting TiO2/SiO2/Fe3O4 nanoparticles activity in photocatalytic degradation of methyl orange were investigated using response surface methodology (SRM). Precipitation method and sol-gel technique were used to prepare SiO2/Fe3O4 electromagnetic composite support and TiO2/SiO2/Fe3O4 photocatalytically active nanoparticles. The specific surface area, pore volume, and average pore size of the synthesized nanoparticles were respectively equal to 56 m2/g, 0.12 cm3/g and 9.4 nm. The point of zero charge (PZC) of the catalyst was measured to be 5.9. The maximum and minimum photocatalytic degradation of methyl orange using the synthesized nanoparticles were 100% and 30%, respectively. A linear model was fitted to the obtained results with R2adjusted equal to 0.87. The results of analysis of variance (ANOVA) revealed that catalyst concentration, reaction media pH and aeration rate were significantly affected the photocatalytic activity. Optimization was performed considering photocatalytic activity as the main objective functions. In order to maximize photocatalytic activity, catalyst loading, reaction media pH and aeration rate were respectively adjusted to 2,000 ppm, 3 and 2.5 L/min, which resulted in total methyl orange removal. Considering promising photocatalytic activity of TiO2/SiO2/Fe3O4 along with core-sell nanocomposite separation performance led us to propose this photocatalyst as an alternative solution for treating waste waters.