Aptamers are single-stranded RNA or DNA ligands that can specifically bind to various molecular targets with high affinity. Owing to this unique character, they have become increasingly attractive in the field of drug delivery. In this study, we developed a multifunctional composite micelle (CM) with surface modification of aptamer AS1411 (Ap) for targeted delivery of doxorubicin (DOX) to human breast tumors. This binary mixed system consisting of AS1411 modified Pluronic F127 and beta-cyclodextrin-linked poly(ethylene glycol)-b-polylactide could enhance DOX-loading capacity and increase micelle stability. Cellular uptake of CM-Ap was found to be higher than that of untargeted CM due to the nucleolin-mediated endocytosis effect. In vivo study in MCF-7 tumor-bearing mice demonstrated that the AS1411-functionalized composite micelles showed prolonged circulation time in blood, enhanced accumulation in tumor, improved antitumor activity, and decreased cardiotoxicity. In conclusion, aptamer-conjugated multifunctional composite micelles could be a potential delivery vehicle for cancer therapy. From the Clinical Editor In this study, a multifunctional composite micelle with surface modification of aptamer AS1411 was used for targeted delivery of doxorubicin to human breast tumors, demonstrating significantly higher tumor volume reduction than doxorubicin alone.