Abstract: Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) is the primary anthraquinone in the roots of rhubarb. A recent study showed that rhein can inhibit tumor cell proliferation and induce apoptosis in human tumor cells. However, the clinical application of rhein has been hampered by its poor bioavailability, low aqueous solubility and gastrointestinal disorders. In current study, twenty-four target compounds were designed and synthesized by coupling various hydrophilic alkanolamines to the 2-carboxyl of rhein, and their structures were established by IR, HR-MS, ¹H NMR spectra. Solubility test showed that all compounds were 10.04 to 15.08 mg·mL^-1 in water, which was 220 to 330-fold better than that of rhein (0.045 6 mg·mL^-1). All of rhein derivatives displayed more potent anti-tumor activity than rhein, and most of them were comparable to adriamycin, particularly, compound 4t exhibited IC₅₀ value of 2.08 μmol·L^-1, more effective than adriamycin (IC₅₀=2.35 μmol·L^-1). Hydroxyapatite adsorption experiment suggests that compound 4t has a better bone affinity than that of tetracycline.