In this study, hyaluronic acid (HA), a natural polysaccharide that can specifically bind to CD44 receptors, was conjugated onto laponite® (LAP) nanodisks for the encapsulation and specific delivery of the anti-cancer drug doxorubicin (DOX) to CD44-overexpressed cancer cells. The prepared LM-HA could encapsulate DOX efficiently and release drug in a continuous manner with pH-responsiveness. In vitro cell viability assay proved that LM-HA had good biocompatibility, and drug-loaded LM-HA/DOX exhibited targeted anti-tumor effects against HeLa cells with CD44 receptors overexpressed. In addition, the flow cytometric detection and confocal laser scanning microscope results confirmed that LM-HA/DOX could be specifically internalized by HeLa cells via CD44-mediated endocytosis. Therefore, the HA-modified LAP nanodisks with high drug loading efficiency, pH-sensitive drug release properties and CD44 targetability might be an efficient nanoplatform for cancer chemotherapy.