DNA-based nanomaterials have attracted increasing attention over the past decades due to their incomparable programmability and functionality. In particular, dendritic DNA nanostructures are ideal for constructing drug carriers due to their highly branched structure. In this study, an intelligent drug delivery system was constructed based on DNA dendrimers, in which the DNA duplexes were utilized for simultaneously loading both hydrophilic and hydrophobic small molecule drugs. Additionally, cancer microenvironment-responsive and cancer cell-targeting moieties were introduced into the internal framework and surface of the nanostructures, respectively. Our research shows that these DNA-based drug carriers can enter cancer cells through endocytosis and disintegrate under the reduction of cellular glutathione, thereby achieving targeted co-delivery and controlled release of chemotherapeutic agents and antisense oligonucleotides, providing an effective drug delivery strategy for combined treatment of tumors.