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In this work, we report the synthesis of a new thiosemicarbazone-based drug of N′-(di(pyridin-2-yl)methylene)-4-(thiazol-2-yl)piperazine-1-carbothiohydrazide (H<b>L</b>) featuring a thiazole spectator for efficient coordination with Cu(II) to give [CuCl(<b>L</b>)]₂ (<b>1</b>) and [Cu(NO₃)(<b>L</b>)]₂ (<b>2</b>). Both <b>1</b> and <b>2</b> exhibit dimeric structures ascribed to the presence of di-2-pyridylketone moieties that demonstrate dual functions of chelation and intermolecular bridging. H<b>L</b>, <b>1</b>, and <b>2</b> are highly toxic against hepatocellular carcinoma cell lines Hep-G2, PLC/PRF/5, and HuH-7 with half maximal inhibitory concentration (IC₅₀) values as low as 3.26 nmol/mL (H<b>L</b>), 2.18 nmol/mL (<b>1</b>), and 2.54 × 10⁻⁵ nmol/mL (<b>2</b>) for PLC/PRF/5. While the free ligand H<b>L</b> may elicit its anticancer effect via the sequestration of bio-relevant metal ions (i.e., Fe³⁺ and Cu²⁺), <b>1</b> and <b>2</b> are also capable of generating cytotoxic reactive oxygen species (ROS) to inhibit cancer cell proliferation. Our preliminary pharmacokinetic studies revealed that oral administration (per os, PO) of H<b>L</b> has a significantly longer half-life <i>t</i>_1/2 of 21.61 ± 9.4 h, nearly doubled as compared with that of the intravenous (i.v.) administration of 11.88 ± 1.66 h, certifying H<b>L</b> as an effective chemotherapeutic drug via PO administration.