CaCO3particles, due to their unique properties such as biodegradation, pH-sensitivity, and porous surface, have been widely used as carrier materials for delivering drugs, genes, vaccines, and other bioactive molecules. In these applications, CaCO3particles are often administered intravenously. In this sense, the interaction between CaCO3particles and blood components plays a key role in their delivery efficacy and biosafety, though the hemocompatibility of CaCO3particles has not been evaluated until now. Deficiency in the biosafety information has delayed the clinical use of CaCO3particles in delivery systems. In this work, we investigated the biosafety of CaCO3particles, focusing on theirin vitroandin vivoeffects on key blood components (red blood cells, platelets, etc) and coagulation functions. We foundin vitrothat high concentrations of CaCO3particles can cause the aggregation and hemolysis of red blood cells, with platelet activation and coagulation prolongation.In vivo, we found that intravenously injected CaCO3particles at 50 mg kg-1significantly disturbed the red blood cells, and platelet-related blood routine indexes, but did not induce visible abnormalities in the tissue structures of the key organs. Overall, these effects may be due to the enormous adsorption capability of the porous surface of CaCO3particles. 0.1 mg ml-1of the CaCO3particles exhibit excellent compatibility for their practical applications. These results would be expected to greatly promote thein vivoapplications and clinical use of CaCO3particles in biomedicine.