In this study, we revealed that CD44-targeted A6 peptide functionalized biomimetic nanoparticles possesses remarkable targetability and anticancer activities toward orthotopic human acute myeloid leukemia xenografts and heterotopic human colon tumor xenografts in vivo, lending to significant survival benefits and avoid hepatotoxicity compared to unmodified nanoparticles as well as free HSP90 inhibitor. This evidence concerns the gene CD44 and colonic neoplasm.