An efficient heterogeneous catalyst (Ni(II)-Vanillin-Schiff base-MCM-41) has been synthesized by immobilization of nickel(II)-vanillin complex on MCM-41 nanostructure and characterized by XRD, TGA, BET, EDS, SEM, ICP-OES, TEM and FT-IR spectroscopy. The catalytic activity and stability of the prepared compound has been studied in some multicomponent reactions with polyhydroquinoline, 1H-indazolo [1,2-b] phthalazine-trione and 2,3-dihydroquinazolin-4(1H)-one derivatives under mild condition reactions. All the reactions were carried out in the presence of water as the solvent and under solvent-free conditions. The simple work up, mild conditions, excellent yield, inexpensive and non-toxic catalyst; makes this protocol both attractive and economically viable. More importantly, this catalyst can be reused several times without any significant loss of its catalytic activity.