Abstract: A series of novel xanthones with terminal amine substituents at xanthone's C3 and C6 positions were designed and synthesized as potential ligands for telomeric G-quadruplex DNA. All the compounds in this series were bound to telomeric G-quadruplex in a "thread intercalation" manner that illustrated both in molecular docking and spectrometric studies. Among them, 10c and 10d showed better binding abilities and specific affinity toward G-quadruplex DNA HTG21 over ctDNA in the fluorescence assay. The antiproliferative activities of four screened compounds were examined in three cancer cells by MTT in vitro, and their inhibitory effects were observed at low micromolar ranges. In addition, the PCR stop assay demonstrated that 10c and 10d effectively inhibited the amplification ability of telomerase.