This study aims to optimize the lipid content of Scenedesmus sp. for high-yield biodiesel production. Three factors affecting the culture conditions, namely salinity, nitrogen concentration, and light intensity, were selected and their effects on the maximum lipid content were investigated using the Box Behnken design. The results showed that the maximum lipid content (32.7% of algal dry weight) was obtained in the algal samples cultured under the optimized conditions. A core-shell magnetic nano-catalyst, NiFe 2 O 4 @SiO 2 /MgO, was synthesized and used to produce biodiesel via the transesterification reaction. The nano-catalyst was characterized by field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray powder diffraction analysis (XRD), vibrating sample magnetometry (VSM), elemental mapping techniques, transmission electron microscopy (TEM), and Fourier transform infrared spectroscopy (FT-IR). Using the Box Behnken design and keeping the temperature constant, the molar ratio of methanol to oil, the amount of catalyst, and the time were optimized to achieve the maximum yield of biodiesel. The maximum yield of biodiesel was 95.3% under the optimal conditions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)