A new amine-functionalized UiO-66/organosilica mixed-matrix membrane was fabricated and explored for pervaporation (PV) water desalination. The incorporation of amine-functionalized UiO-66 (UiO-66-NH2) into the BTESE-derived organosilica networks endowed the membrane with enhanced hydrophilicity and dense network structure, leading to an improvement in water flux and NaCl rejection. The UiO-66-NH2/BTESE mixed-matrix membrane was proved to be highly effective for desalination of saline water in concentrations from 1 to 13 wt% of dissolved NaCl. Moreover, the membrane exhibited superior structural stability under a continuous PV desalination operation up to 100 h, delivering water permeance of >3.1 × 10−6 mol m−2 s−1 Pa−1 combined with NaCl rejection of >99.9%. The high water permeance was mainly ascribed to the specific pore structure and the preferential interactions between pore channels and water molecules, and the excellent salt rejection was primarily based on the sieving effect. The proposed UiO-66-NH2/BTESE mixed-matrix membranes show great prospects as an alternative for concentrated brine desalination.