Fast water permeable filters with an efficient rejection ratio are desirable for nanoparticle separation and water/air purification. Ultrathin nanoporous filters are effective because of their features, including narrow and tunable pore size distributions capable of handling a high solvent flux. However, it remains challenging to develop antifouling filters that maintain a stable flux with high rejection efficiency over long-term filtration of nanoparticle solutions. Here, a facile and low-cost approach is reported to fabricate biocompatible hydrogel filters with interconnected nanofiber network structures through the use of high aspect ratio, wood-derived nanofibrillated cellulose (NFC). The super-hydrophilia and high porosity of these materials endow the NFC hydrogel filters (NFC-HFs) with high solvent permeance. Nanofibrous networks and interconnected nanoporous structures of NFC-HFs promote efficient rejection and precise size-selective separation of nanoparticles. Specifically, small and irregular nanopores of NFC-HFs fail to match the size of relatively large nanoparticles, which ensures a relatively stable flux of the NFC-HFs over the whole filtration process, even under continuous filtration of highly concentrated nanoparticle solutions.