Nanoscale calcium carbonate powder is a very important engineering material used for packaging and polymer-based composite additive. The surface hydrophobic modification of nanoscale calcium carbonate is achieved by three silane coupling agents of APTES, MPTES and KH570, respectively. The Fourier Transform Infrared Spectrometry (FT-IR) is used to confirm the surface chemical coupling variations, and the contact angle instrument to determine its hydrophobicity. After KH570 modification, the sample of nanopowder shows the best hydrophobicity of a contact angle of 107 °. The findings are of significance to enhance its dispersity and compatibility in organic media.