Introducing multiclusters and multiligands (mm) in a well-defined array will greatly increase the diversity of metal-organic frameworks (MOFs). Here, a series of porous mm-MOFs constructed from a pillared-layer and pore-space partition (PL-PSP) have been achieved. FJU-6 with {Co-3}-cluster-based sheets and {Co-6}-cluster-based pillars exhibits new (3,9,12)-connected llz topology. By using the substituted analogues of the ligands and metal ions, seven isoreticular mm-MOFs (FJU-6-X, X = PTB, TATB, Me-INA, F-INA, NDC, BrBDC, Ni) have been synthesized with the adjustable BET surface areas ranging from 731 to 1306 m(2)/g as well as the adsorption capacity of CO2 increasing by 77%. The C2H2/CO(2 )mixture can be effectively separated in the breakthrough experiments in the fixed bed filled with solid FJU-6-TATB at ambient temperature. In all, integrating pillared-layer strategy and pore-space partitioning is effective at constructing mm-MOFs with multivariate environments for the optimization of gas adsorption and separation.