A novel Sm III complex [Sm III (LA) 2 (pic) 3 ] (Hpic = picric acid), in which LA is a natural-derived alkaloid, liriodenine, was synthesized and characterized by IR, elemental analysis, and single-crystal X-ray diffraction analysis. This complex showed enhanced solubility compared with liriodenine and its metal complexes that have been previously reported. The interaction of the Sm III complex with ct-DNA was further investigated by various spectroscopic techniques, such as UV/Vis spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy (CD), and viscosity measurement. The results showed that the intrinsic binding constant K b of the Sm III complex with ct-DNA was calculated to be 5.03 ϫ 10 3 L·mol -1 by UV/Vis absorption spectral analysis. The thermodynamic fluorescent spectral analysis 570 suggested that the fluorescence intensity of the Sm III complex was weakened by ct-DNA mainly through a dynamic quenching mechanism. The presence of Sm complex could increase the viscosity of DNA solution, so it was concluded that the complex bound with ct-DNA via a moderate intercalative mode. Furthermore, this Sm III complex exhibited significant growth inhibition on the three typical tumor cell lines, HepG2, T-24, and SK-OV-3, with the corresponding IC 50 values, 10.76 Ϯ 0.19, 8.85 Ϯ 1.12, and 10.01 Ϯ 0.55 μM, respectively. The in vitro antitumor activity was comparable with LA and cisplatin, which suggested that it might be a new broad spectrum antitumor agent with more satisfying solubility. Scheme 1. Chemical structure of the natural alkaloid, liriodenine.