We report on the therapeutic ability of a novel cyclodextrin-covered gold nanoparticle (AuNP) carrier for noncovalent encapsulation of an anti-cancer drug. The surface of the AuNPs was functionalized with cyclodextrin as a drug pocket, anti-epidermal growth factor receptor (anti-EGFR) antibody as a targeting moiety, and poly(ethyleneglycol) (PEG) as an anti-fouling shell. b-Lapachone, an anticancer drug, was efficiently encapsulated into the hydrophobic cavity of cyclodextrin on the surface of the AuNP carriers (AuNP-1). The glutathione-mediated release of b-lapachone from the surface of AuNP-1 was demonstrated by an experiment with MCF-7 (low glutathione concentration) and A549 cells (high glutathione concentration). We also show that the introduction of an anti-EGFR antibody onto the AuNP carriers (AuNP-2) increased the intracellular uptake of AuNP carriers as compared with AuNP-1, which does not contain a targeting ligand. In the in vitro cytotoxicity study, AuNP-2 with b-lapachone exhibited a higher apoptosis effect than that caused by AuNP-1 with b-lapachone. This work suggests that AuNPs covered with cyclodextrin and tumor-targeting ligands may find useful applications for the development of nanoparticles with therapeutic and diagnostic modalities.