The side effects or toxicity of cyanoacrylate used in vivo have been argued since its first application in wound closure. We propose an airflow-assisted in situ precision electrospinning apparatus as an applicator and make a detailed comparison with traditional spraying via in vitro and in vivo experiments. This novel method can not only improve operational performance and safety by precisely depositing cyanoacrylate fibers onto a wound, but significantly reduce the dosage of cyanoacrylate by almost 80%. A white blood cell count, liver function test and histological analysis prove that the in situ precision electrospinning applicator produces a better postoperative outcome, e.g., minor hepatocyte injury, moderate inflammation and the significant ability for liver regeneration. This in situ precision electrospinning method may thus dramatically broaden both civilian and military applications of cyanoacrylates.