Metal nanoparticles (NPs) stabilized by metal-organic frameworks (MOFs) are very promising for catalysis, while reports on their cooperative catalysis for a cascade reaction were very rare. In this work, Pd NPs incorporated into a MOF, MIL-101, have jointly completed a tandem reaction based on MOF Lewis acidity and Pd NPs. Subsequently, ultrafine PdAg alloy NPs (~1.5 nm) have been encapsulated into MIL-101. The obtained multifunctional PdAg@MIL-101 exhibits good catalytic activity and selectivity in cascade reactions under mild conditions, based on the combination of host-guest cooperation and bimetallic synergy, where MIL-101 affords Lewis acidity, Pd offers hydrogenation activity while Ag greatly improves selectivity to the target product. As far as we know, this is the first work on bimetallic NPs@MOF as a multifunctional catalyst with multiple active sites (MOF acidity and bimetallic species) that exert respective function and cooperatively catalyze a one-pot cascade reaction.