Inspired by the bio-conjugated compounds, herein we report the synthesis of madecassic acidsilybin conjugates with an ester bond between a hydroxy group of silybin and the carboxyl group of madecassic acid, or over an amino acid as a spacer, and evaluation of their antiproliferative in vitro potential against the HepG2 human liver cancer cell line. The most potent active compound 8 was further evaluated for cytotoxic activity on the Hep3B, Huh7, and Huh7R liver cancer cell lines together with cell cycle analysis.