The binding of three stereoisomers of cyclocantharidatoplatin, RS, RR and SS, with calf thymus DNA was investigated by ITC, DSC, CD and NMR methods. The enthalpy changes for the binding of three stereoisomers of cyclocantharidatoplatin with DNA are - 1. 1 (RS ), - 7.2 (RR) and 16 (SS) kJ•mol - 1 at 298. 15K, respectively. In the presence of three stereoisomers of cyclocantharidatoplatin, the melting temperatures of DNA are 346. 72(RS),350. 82(RR) and 351. 69 K(SS), respectively, compared with the melting temperature 343. 16 K of DNA. The CD spectra of the DNA binding with three stereoisomers of cyclocantharidatoplatin at room temperature show a small difference of molar ellipticity between them and that of DNA. Comparing the 1H-NMR spectra of SS -cyclocantharidatoplatin in the presence of DNA with that in the absence of DNA at room temperature, there is no distinct difference between them. On the basis of the above experimental results, the binding model of cyclocantharatoplatin with DNA has been discussed.