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Developing low-migration macromolecular photoinitiators (macro PIs) is significant to achieve a sufficient biosafety for photopolymers. In this study, for the first time lignin was introduced into photoinitiating systems. A novel lignin-based water-soluble macro PI (L-PEG-2959) was designed and synthesized by introducing water-soluble PEG chain and photoinitiating moiety into lignin backbone simultaneously. A series of characterizations were performed, including 1H NMR, FTIR, UV–vis, GPC, and TGA analysis, which indicated that L-PEG-2959 has excellent light absorption property within 200–400 nm, high initiating efficiency, and superior water solubility. Additionally, L-PEG-2959 could be compatible well with glycidyl methacrylate-modified gelatin (Gel-GMA) and initiate the photopolymerization of Gel-GMA quickly under UV irradiation to form a chemical cross-linking hybrid hydrogel. Compared with the neat hydrogel prepared by Gel-GMA initiated with Irgacure2959, a commercial small molecular PI, the hybrid hydrogels presented controllable swelling property, increased mechanical strength, remarkably reduced precipitates, and enhanced biosafety. The results indicated the great potential of lignin-based macro PIs in preparing biosafety photopolymers.