Effective hemorrhage control is vital for reducing mortality after major trauma both in civilian life and in the military. In recent years microporous starch (MS) has been used as a hemostatic agent. However, MS has an insufficient hemostatic capacity to stop severe bleeding. To improve its hemostatic performance, in this study calcium-modified microporous starch (CaMS) was firstly developed via oxidization and self-assembly with calcium ions (Ca2+) on MS, and the hemostasis efficiency and degradation behaviour were evaluated. The results showed that the carboxyl groups and Ca2+ had been modified successfully onto MS. MS and CaMS both initiated the hemostatic response by rapid absorption and swelling due to their porous structure and high surface area. It is noteworthy that CaMS activated an intrinsic pathway of coagulation cascade and induced platelet adhesion because of the modified Ca2+ and carboxyl groups. The synergistic effects of the chemical activation mechanism and physical absorption mechanism resulted in a dramatic improvement in the hemostatic capacity of CaMS, and thus achieved an effective hemorrhage control in rabbit liver and femoral artery injuries. Additionally, the degradation of CaMS was improved greatly by the modification. In conclusion, CaMS effectively improved hemostatic performance and degradability. CaMS is a promising candidate for designing hemostatic agents in more extensive clinical applications.