Abstract: OBJECTIVE To synthesize miltirone ester derivatives with various lipid/water partition coefficients based on modification of quinone group, and evaluate the anti-tumor activities. METHODS Hydrogenation reduction, anhydride acylation and deprotection of Boc-groups were used to modify abietane o-quinone sites through introducing different anhydride, amino acid substituents and different miltirone C cyclic phenol ester derivatives were synthesized, on the basis of this, the anti-tumor activity of parts of compounds were evaluated by prostate cancer Lncap and Du145 cell lines. RESULTS Totally 9 miltirone derivatives were synthesized, among which 1 compound exhibited enhanced in vitro anti-tumor activities against Lncap and Du145 cell lines compared with miltirone. CONCLUSION The lipid/water partition coefficient has great influence on the anti-tumor activity of miltirone derivatives, structure modification to improve the hydrophilicity of miltirone can effectively enhance it's antitumor activity.