Rapid control of bleeding is of great significance in military trauma and traffic accidents. In this study, alkylated chitosan (AC) and diatom biosilica (DB) were combined to develop a safe and effective hemostatic composite sponge (AC-DB sponge) for hemorrhage control. Due to the procoagulant chemical structure of AC-DB sponge, it exhibited rapid hemostatic ability in vitro (clotting time was shortened by 78% than that of control group), with favorable biocompatibility (hemolysis ratio < 5%, no cytotoxicity). The strong interface effect between AC-DB sponge and blood induced the erythrocyte and platelets activation, deformation and aggregation, intrinsic coagulation pathway activation, resulting in significant coagulation acceleration. AC-DB sponge had excellent performance in in vivo assessments with shortest clotting time (106.2 s) and minimal blood loss (328.5 mg). All above results proved that AC-DB sponge had great potential to be a safe and rapid hemostatic material.