Cells execute mesmerizing functions using supramolecular polymers (SPs) formed through the self-assembly of biological precursors. Integration of the vast array of synthetic SPs with living cells would offer a powerful way to remold cellular functions and bridge the gap between synthetic materials and the biological realm, yet remains a challenge because of the lack of robust abiotic SP systems that can be triggered to self-assemble inside cells. Here, we report how fully abiotic SPs can be synthesized inside living cells via an organocatalysis-responsive self-assembly strategy, and how the in situ-generated SPs are capable of interfering and can interfere with cellular functions. The incorporation of a nucleophilic organocatalyst (CAT) into living cells accelerates the intracellular conversion of hydrazide (H) and aldehyde-derived precursors (A) to hydrazone-based monomers (HA3) that locally self-assemble into SPs. Interestingly, the in situ-generated SPs possess ignorable effects on cell viability and proliferation but remarkably hinder cell migration. Furthermore, the presence of SPs is found to retard intracellular diffusion and alter the organization of the actin cytoskeleton, both of which are suggested to be responsible for the hindered cellular migration. In considering the vastly wide range of synthetic SPs, tremendous non-natural cellular functionalities can be obtained by in situ-synthesizing SPs.