Flexible electronics based on cellulose paper have attracted a new surge of interest over the past decades due to their eco-sustainable, renewable, and scalable roll-to-roll manufacturing features. However, the application of traditional paper in flexible electronics is hindered by its inferior stability against heat and water, weak mechanical strength, and its large surface roughness and porosity usually result in a poor circuit continuity. Herein, the hot-pressing induced space-confined flow was adopted to drive the melted lignin spread along the cellulose nanofiber (CNF) chains, then the silastic was further integrated into the lignin uniformly coated CNF membrane to construct a silastic-nanopaper substrate for flexible and stretchable electronics. Attributed to the lignin-induced interfacial molecular bridge, the enhanced hydrogen bonding between lignin and CNF, and the adhesive interaction between lignin and silastic, the developed silastic-nanopaper demonstrates an impressive tensile strength (∼380 MPa), toughness (52.75 MJ/m³), and elongation (16.2 %), much superior to the pure CNF (200 MPa, 4.12 MJ/m³, and 3.0 %, respectively). The silastic-nanopaper also shows a low surface roughness (∼3 nm), high wet strength (>350 MPa) and thermal stability (with the maximum decomposition temperature of 480 °C), good UV-blocking capacity, and tunable transmittance haze. The electronic sensor fabricated based on such silastic-nanopaper exhibits a highly sensitive and reliable piezoresistive response to persistent stretching and twisting. The strategy of combining the advantages of lignocellulose and PDMS paves the way for the cost-effective, easy-to-operate manufacturing of electronic substrates.