A novel magnetic mesoporous MCM-41 supported boric acid [Fe3O4@MCM-41-OB(OH)2] is prepared, characterized and its catalytic application is investigated. The Fe3O4@MCM-41-OB(OH)2 was prepared through modification of magnetic iron oxide nanoparticles with MCM-41 silica followed by treatment with boric acid. This nanocomposite was characterized using Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX) and vibrating sample magnetometer (VSM). The Fe3O4@MCM-41-OB(OH)2 was used as effective nanocatalyst in the one-pot Biginelli condensation of aldehydes with urea and alkylacetoacetates at 50 °C under ultrasonic conditions. The corresponding products were obtained in high yields (88–96%) at short times (15–30 min). The designed catalyst was successfully reused and recovered at least nine times without significant decrease in its stability and efficiency.