Abstract: Cantharidine is known to have certain degree of efficacy for the treatment of cancer. The adverse effects on urinary and gastrointestinal tracts prevent it to be accepted by the clinic. The structural modification of cantharidine is pursued by the authors with the aim to decrease its toxicity and increase its efficacy. Thirty one derivatives of Cantharidine with the following types Ⅲ, Ⅳ, Ⅴ, Ⅵ were synthesized. The compounds prepared were listed in tables 1～4Compounds 1～5 were obtained by condensation of Cantharidine with corresponding aliphatic amines in ethyl alcohol. Under the same conditions no reaction occurred with heterocyclic and aromatic amines. Compounds 6～14 were obtained by condensation of cis-7-oxabicyclo 2.2.1-hept-5-ene-2,3-dicarboxylic anhydride with different amines in water or alcohol.Compounds 15～23 were carried out by condensation of bicyclo 2.2.1 hept-5-ene-2,3-dicarboxylic anhydride with pertinent amines.Compounds 24～31 were prepared by condensation of N-amino-cantharidinimide with different aldehydes in ethyl alcohol. The compounds 13,14 and 23 were obtained by bromination of the condensation product in ice bath below 35℃.Results of animal screening rev ealed compounds 2,3 and 4 to be effective against mouse liver carcinoma(ascites) and reticulosarcoma (ascites). Others showed no signi ficant activity. Compound 3 N-hydroxycantharidinimide, has been recommended for clinical trial. Further inves-tigations on 3 are in progress.