In the present work, Fe3O4/SiO2/TiO2 nano-photocatalyst with a core-shell structure was successfully used for the removal of Methylene Blue (MB) as a model organic pollutant from water. The resultant nanoparticles were characterized by X-ray diffraction, field emission scanning electron microscopy, Fourier-transform infrared spectroscopy, vibrating sample magnetometry, Brunauer-Emmett-Teller method, and Barrett-Joyner-Halenda method. Response surface methodology (Box-Behnken approach) was applied to optimize the removal of MB from water. This optimization was used to evaluate the effect of experimental variables and their interaction in achieving the optimum conditions in removal of MB from water which was measured via UV-visible spectroscopy. The optimum conditions were found to be at Si/Fe3O4 wt% = 17.35%, Ti/Fe3O4 wt% = 50.17%, and calcination temperature = 392 degrees C with a 91.1% removal efficiency. Finally, a model was established and the predicted results from the model fitted well with the experimental values indicating that the optimization was successful.