Cellulose-based triboelectric nanogenerators (TENGs) have gained increasing attention. In this study, a novel method is demonstrated to synthesize cellulose-based aerogels and such aerogels are used to fabricate TENGs that can serve as mechanical energy harvesters and self-powered sensors. The cellulose II aerogel is fabricated via a dissolution-regeneration process in a green inorganic molten salt hydrate solvent (lithium bromide trihydrate), where. The as-fabricated cellulose II aerogel exhibits an interconnected open-pore 3D network structure, higher degree of flexibility, high porosity, and a high surface area of 221.3 m g. Given its architectural merits, the cellulose II aerogel-based TENG presents an excellent mechanical response sensitivity and high electrical output performance. By blending with other natural polysaccharides, i.e., chitosan and alginic acid, electron-donating and electron-withdrawing groups are introduced into the composite cellulose II aerogels, which significantly improves the triboelectric performance of the TENG. The cellulose II aerogel-based TENG is demonstrated to light up light-emitting diodes, charge commercial capacitors, power a calculator, and monitor human motions. This study demonstrates the facile fabrication of cellulose II aerogel and its application in TENG, which leads to a high-performance and eco-friendly energy harvesting and self-powered system.