Abstract A catalytic system based on Pd−Ni bimetallic nanoparticles (BMNPs) encapsulated in the nanocavities of UiO‐66 was established for the activation of C−O bonds in ethers. Pd0.25Ni4@UiO‐66 catalyst show excellent catalytic performance in the directly methylation and arylation of ethers under a mild reaction condition. High catalytic activity of the catalyst could be ascribed to the “synergistic effect” between the two metal components and strong interaction between BMNPs and the carrier (UiO‐66). BMNPs encapsulated in UiO‐66 also guarantee a good reusability of the catalyst, the catalyst delivered high catalytic activity for at least four cycles. Our work highlights the great potential value of ethers as powerful alternatives for aryl halides as well as the bright future of BMNPs and MOFs in the catalysis field.