It is challenging to develop an in vitro catalytic system to conduct natural surface-confined enzymatic reactions in a stable, efficient, and spatially defined manner. Here, we report that an artificial catalyst, which composes of trypsin and a calcium ion exchanged zeolite Y (trypsin/CaY), is capable of conducting surface-confined thrombin generation, and then constructs an artificial shortcut for classic, natural and complex blood coagulation cascade. The Ca²⁺ within the microporous cages play a key role in trypsin/CaY hybrid through tuning the bio-inorganic interaction and spatial orientation of the protease, which allows trypsin/CaY to display greatly enhanced catalytic performance in coagulation process. The in vivo efficiency of the artificial coagulation shortcut is further confirmed in massive bleeding and hemophilia animal models. Rapid hemostasis is achieved by trypsin/CaY hybrid in a hemophilia A mice tail bleeding model, where natural clotting system fails in response to bleeding event due to factor VIII deficiency. In a rabbit lethal femoral artery injury model, the blood loss of the artificial catalyst is decreased by 4-7 fold when compared to state-of-art clay- or zeolite-based topical agents.