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The interaction between copper (II) complex with piroxicam (Pir) as ligand, trans-(Cu (Pir)2(DMF)2) and calf thymus deoxyribonucleic acid (ct-DNA) using UV/Vis absorption spectroscopy, fluorescence quenching study, thermal melting of ct-DNA and thermodynamic studies was investigated. Spectrophotometric studies showed that the binding constant was Kb = 3.3104×105 M-1at 298 K. A competitive binding with ethidium bromide (EB) showed that trans-(Cu (Pir)2(DMF)2) displace EB from its binding site in ct-DNA. The thermal denaturation experiments show the melting temperature of ct-DNA increases (about 0.5°C) due to binding of trans-(Cu (Pir)2(DMF)2). The thermodynamic parameters were calculated by van't Hoff equation and indicated that electrostatic and van der Waals play major roles in the interaction. All of the experimental results show that the outside bindingmust be predominant.