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Porous organic framework materials such as hypercrosslinked polymers (HCP) show a high chemical stability and dynamic behavior in a variety of solvents while their pore properties exhibit great potential for mixed matrix membrane (MMM) applications. However, their influence as porous filler in MMMs, especially for applications in liquid-phase filtration is still unexploited. Herein, we demonstrate an HCP-based MMM for molecular separation in the liquid phase by nanofiltration (NF). Depending on the solvent, the membrane changes its fractional free volume by shrinking or swelling. In connection to that, the pore size is also influenced, hence, providing a tunable permeance and molecular cut-off. The reduction of the pore volume and size directly correlates to the improvement of the NF performance, while the volume increase completely diminishes it. The extraordinary flexibility and high degree of crosslinking assure permanent porosity and render the dynamic behavior fully reversible. Thereby, a solvent-responsive “on” and “off” switching of the NF properties is enabled and was experimentally proven. Overall, this provides alternative strategies regarding the fouling and regeneration of membranes as well as the inhibition of pore blocking in membrane-derived processes by a tunable separation performance.