A chiral ruthenium(II) complex, Λ-[Ru(bpy)₂(o-tFMPIP)] (ClO₄)₂ (o-tFMPIP = 2′-trifluoromethylphenyl) imidazo [4,5-f][1,10]phenanthroline, was prepared and evaluated for its enhancement of the radiosensitivity of ¹²⁵I seeds. The synthetic Ru(II) complex, LR042, effectively enhanced growth inhibition against HepG2 human hepatocellular liver carcinoma cells induced by ¹²⁵I seeds and consequently effectively promoted the apoptosis of tumor cells with increasing level of cleave-caspase-3. Furthermore, the results of immunofluorescence indicated that LR042 enhanced the phosphorylation of H2AX by ¹²⁵I seeds vigorously in response to damaged DNA. LR042 improved DNA damage induced by ¹²⁵I seeds, which resulted in apoptosis through the activation of the p53/AKT signal. In conclusion, synthetic LR042 can be further developed as a potential radiosensitizer of ¹²⁵I seed radiotherapy for cancer therapy.