Uncontrolled bleeding remains one of the direct causes of high mortality. There is an urgent need for developing emergency hemostats capable of coping with uncontrolled bleeding. The commercial starch-based hemostatic powder (PerClot®) requires compression during application, which limits its application in hemostasis of irregular and non-compressed wounds. Herein, a boronic acid-modified thiol starch sponge (St-SP sponge) with self-gelling properties was developed for hemorrhage control. The results show that the St-SP sponge could quickly absorb blood, self-gel and self-heal to seal the bleeding sites. In addition, the St-SP sponge can rapidly initiate the coagulation cascade and promote the adhesion and aggregation of erythrocytes and platelets. The St-SP sponge exhibited significantly improved in vitro and in vivo hemostatic abilities as compared with PerClot. Notably, the St-SP sponge attained complete hemostasis without any compression in 61.5 s and made a great difference compared to PerClot (169 s) for the irregular wound constructed on the rabbit liver. In addition, the St-SP sponge had good hemocompatibility and cytocompatibility. It turns out that the newly developed St-SP sponge is a promising material for first-aid hemostasis of irregular and non-compressed wounds.