Lignin nanospheres (LNPs) are an emerging high-value material platform to realize lignin valorization. The modification or introduction of new functions to LNPs is of great significance to expand its downstream applications. This work evaluated the technical feasibility of preparing lignin–xylan hybrid nanospheres (LXNPs) through a simple solution-based self-assembly process, with the goal of achieving the application as pesticide carriers for enzyme-mediated controlled release. Hybrid LXNPs with various weigh ratios (lignin to xylan, 3 : 1, 1 : 1, 1 : 3) were obtained using deep eutectic solvent-extracted condensed lignin and water-insoluble xylan fragments, which exhibited a nanosphere size of about 166–210 nm with considerable stability in the pH range of 4–10. LXNPs with lignin to xylan ratios of 3 : 1 and 1 : 1 showed well-defined core–shell structures with enriched hydroxyl groups on the surface. It was proposed that lignin could anchor xylan fragments through van der Waals force and hydrophobic interactions between lignin phenylpropanes and xylan molecular backbones, thus facilitating the self-assembly process for the formation of this specific spherical structure. The resulting hydrophobic LXNPs core enabled the facile encapsulation of the biological pesticide avermectin (AVM) with 57.9–67.0% efficiency using one-pot synthesis. When these AVM-encapsulated LXNPs were subjected to enzymatic hydrolysis using xylanase, considerable AVM release of 44.8–55.1% was achieved after 16 h, in comparison to the 4.1% release only for those without xylanase. This work showed the high promise of fabricating hybrid LXNPs through the self-assembly process and also provided a universal nanosphere carrier for drug encapsulation and subsequent enzyme-mediated controlled release.