DNA can be used to nanofabricate three-dimensional (3D) polyhedra. A variety of applications of 3D DNA assemblies have been proposed. Drug encasulation and intracellular delivery using DNA nanoparticles, however, have remained a challenge. Here, we create a distinct five-point-star motif and aptamer-conjugated six-point-star motif using well-used primer sequences to intermolecularly construct DNA icosahedra as a nanocarrier for doxorubicin. Aptamer-conjugated doxorubicin-intercalated DNA icosahedra (Doxo@Apt-DNA-icosa) show an efficient and specific internalization for killing epithelial cancer cells.