Nanoparticular drug delivery systems may help to overcome the limitations of conventional chemotherapy. They have been reported to improve the specificity of distribution, the bioavailability, and the solubility of drugs, as well as the duration of drug efficacy, and helping to overcome multidrug resistance. Although various polymeric nanoparticles have been developed for delivery of anticancer agents, most nanoparticles still focus on solubilizing drugs, improving targeting ability, and reducing side effects. In particular, targeting to the tumor is typically improved through passive or active targeting. Despite great achievements in both strategies, yet to be resolved are issues of toxicity in normal cells and enhancement of tumor-specificity. A new approach combining the dual strategies of passive tumor targeting and cancer-selective efficacy is proposed. Recombinant human gelatin conjugated with lipoic acid (rHG-LA) developed in this study forms nanoparticles spontaneously in aqueous solution and encapsulates alpha-tocopheryl succinate (a-TOS), a well-known cancer-selective apoptosis-inducing agent, within a hydrophobic core during the self-assembly. This study describes the promising applicability of a-TOS-loaded rHG-LA nanoparticles with passive targeting ability and cancer-specificity.