Abstract: The determination of C-reactive protein (CRP) by liquid chromatography-isotope dilution mass spectrometry（LC-IDMS） was developed. As the potential value assay method for CRP pure certified reference material (CRM), the isotope labeled leucine and valine were selected as internal standard added into the CRP samples. The samples were separated by Zorbax SB-Aq column, and measured by tandem mass spectrometer equipped with an electrospray ionization source operated in multiple reaction monitoring (MRM) mode. The determination of uncertainty was calculated and analyzed, the measured results were (41.5±0.9) mmol/kg. International comparison of Japan, South Korea and China was carried out by this method and obtained the equivalent comparison results.