Uncontrollable bleeding is the main cause of death during surgical trauma and accidental injuries. To halt the bleeding caused by arterial rupture is still challenging due to the high pressure and velocity of arterial blood flow. Enzyme-responsive hydrogels have emerged as promising solutions for hemostasis after arterial rupture, largely due to their high hemostatic efficiency and specificity. However, the existing enzyme-responsive hydrogels suffer from weak cross-linking. Here, we report the design of a hemostatic material with nanoporous, combining a transglutaminase enzyme reaction and Schiff base reaction, for percutaneous injection. Here, we show that the resulting burst pressure of the hemostatic material was 134 ± 10 mmHg, which is significantly greater than the normal systolic blood pressure. Most importantly, the material was able to efficiently stop the bleeding a pig and rat arterial vessel models, with a ~10 s gelling time and without the need for the hemostatic clamps on both ends of the vessel injury. Furthermore, the hemostatic material functioned as an anti-adhesion barrier in a rat liver model. The present study describes an effective, injectable hydrogel solution for the rapid and minimally invasive hemostatic treatment of bleeding diseases in parenchymal organs.