In recent two decades, considerable efforts have been devoted to the room-temperature green syntheses of metal-organic frameworks (MOFs) to reduce energy consumption and increase safety. It could improve some properties (e.g., catalysis, gas adsorption) and facilitate the utilities of sensitive compounds. Herein, the magnetic hybrid catalyst (Fe3O4@MOF-5) was synthesized through a mixing procedure at room temperature and confirmed by various techniques. The SEM images exhibit cubic crystals that were uniformly coated by the Fe3O4 cores. Then, the catalytic ability of Fe3O4@MOF-5 was studied in the green synthesis of tetrahydropyridines via a domino multi-component reaction, which led to the desired products with high yield. Magnetic solid properties make it easily separated from the reaction medium, so the proposed catalyst can be reused five times while maintaining the catalytic activity over 80%.