AbstractConventional tissue adhesives face challenges for hemostasis and tissue regeneration in large‐scaled hemorrhage and capillary hypobaric bleeding due to weak adhesion, and inability to degrade at specific sites. Herein, convenient and injectable poly(ethylene glycol) (PEG)‐based adhesives are developed to address the issues for liver hemostasis. The PEG‐bioadhesives are composed of tetra‐armed PEG succinimide glutarate (PEG‐SG), tetra‐armed PEG amine (PEG‐NH₂), and tri‐lysine. By mixing the components, the PEG‐bioadhesives can be rapidly formulated for use of liver bleeding closure in hepatectomy. The PEG‐bioadhesives also possess mechanical compliance to native tissues (elastic modulus ≈40 kPa) and tough tissue adhesion (≈28 kPa), which enables sufficient adhering to the injured tissues and promotes liver regeneration with the PEG‐bioadhesive degradation. In both rats of liver injury and pigs of large‐scaled hepatic hemorrhage, the PEG‐bioadhesives show effective hemostasis with superior blood loss than conventional tissue adhesives. Due to biocompatibility and degradability, the PEG‐bioadhesive is advantageous for liver regeneration, while commercial adhesives (e.g., N‐octyl cyanoacrylate) display adhesion failure and limited liver reconstructions. These PEG‐bioadhesive components are FDA‐approved, and demonstrate excellent adhesion to various tissues not only for liver hemostasis, it is a promising candidate in biomedical translations and clinical applications.