Herein, we reports the application of various spinel ferrite nanoparticles, MFe2O4 (M = Co, Ni, Cu, Zn), as efficient catalyst for Biginelli reaction. All ferrite nanoparticles were synthesized using a novel aqueous solution based method. It was observed that, the catalytic activity of the ferrite nanoparticles followed the decreasing order of CoFe2O4 > CuFe2O4 > NiFe2O4 > ZnFe2O4. The most important feature of these ferrite nanocatalysts is that, these nanoparticles can directly be used as catalyst and no surface modification or functionalization is required. These ferrite nanoparticles are easily separable from reaction mixture after reaction by using a magnet externally. Easy synthesis methodology, high catalytic activity, easy magnetic separation and good reusability make these ferrite nanoparticles attractive catalysts for Biginelli reaction.