A new low-pressure plasma-based approach to activate the surface of BN nanoparticles (BNNPs) in order to facilitate the attachment of folate acid (FA) molecules for cancer-specific therapy is described. Plasma treatment of BNNPs (BNNPs^PT) was performed in a radiofrequency plasma reactor using ethylene and carbon dioxide monomers. The carboxyl groups deposited on the surface of BNNPs^PT were activated by N,N’-dicyclohexylcarbodiimide (DCC) and participated in the condensation reaction with ethylene diamine (EDA) to form a thin amino-containing layer (EDA-BNNP^PT). Then, the DCC-activated FA was covalently bonded with BNNPs^PT by a chemical reaction between amino groups of EDA-BNNPs^PT and carboxyl groups of FA. Density functional theory calculations showed that the pre-activation of FA by DCC is required for grafting of the FA to the EDA-BNNPs^PT. It was also demonstrated that after FA immobilization, the electronic characteristics of the pteridine ring remain unchanged, indicating that the targeting properties of the FA/EDA-BNNPs^PT nanohybrids are preserved.