In order to improve the compatibility and dispersion of anhydrous calcium sulfate whiskers (ACSW) in polymer composites, the treatment for surface modification was studied with aqueous solution sodium stearate (SS, C17H35COONa) at hot temperature. The surface modification mechanism between stearate and ACSW was carried out by experimental and density functional theory (DFT) simulation. The surface property of modified anhydrous calcium sulfate whiskers (M-ACSW) became hydrophobic by changing the water contact angle with the calcium sulfate whisker (CSW) from 0 degrees to 132 degrees. The TEM and TG results proved the adsorption of stearate on M-ACSW surface, which was further confirmed by FTIR and XPS. The experimental and DFT simulation outcomes for the mechanism were interpreted by taking the reaction of the carboxyl group of stearate with Ca2+ ions to form calcium stearate on the whisker surface. Their long alkyl chains of stearate coated on the surface of whisker made ACSW improve the surface with a hydrophobic property. Thus, here it is provided details of a novel method of modifier selection for CSW and its interaction mechanism with the crystal surface.