The targeted delivery of chemotherapy drugs to tumor lesions is a major challenge for the treatment of tumors. Up until now, various polymeric nanoparticles have been explored to improve the targetability of these therapeutic drugs through passive or active targeting processes. In the design and construction of polymer nanoparticles, glycopolypeptide has shown great potential owing to its excellent targeting ability and biocompatibility. In order to enhance the antitumor effect of doxorubicin (DOX), a glycopolypeptide-based micelle (GPM) modified by α-lactose (Lac) was synthesized for targeted treatment of hepatoma. The DOX-loaded GPM (i.e., GPM/DOX) could significantly target human hepatoma (HepG2) cells and further inhibit their proliferation in vitro. Additionally, GPM/DOX exhibited a much higher drug accumulation in tumor tissue and a stronger antitumor effect in vivo than free DOX. The above results revealed that this drug delivery system provides a promising platform for the targeting therapy of hepatic cancer.