Abstract: Spectrophotometric titrations were performed in aqueous buffer solution (pH=3.0,pH=10.5) at 25℃ to determine the binding constants of cyclodextrins and its derivatives with podophyllotoxin guest molecules.The results indicate that podophyllotoxin with cyclodextrins and its derivatives in alkaline conditions (pH=10.5),the binding constant are relatively large.Podophyllotoxin is more stable in alkaline conditions under the formation of inclusion complexes;the molecular inclusion ability is dominated by the size/shape-matching between host and guest,the size/shape of γ-CD cavity and guest molecules podophyllotoxin are well matched,so the Ks is maximum.In addition,the substituent on the β-CD derivatives changes its original binding ability,podophyllotoxin with methylated β-CD form the inclusion complex,the methoxy is substituted more on β-CD,less well to the inclusion formation.