Objective:　To　design　and　synthesize　a　series　of　novel　ursolic　acid　(UA)　derivatives　bearing　different　kinds　of　charge　and　to　study　their　in　vitro　anti-tumor　activities.　Methods:　Ursolic　acid　derivatives　bearing　different　charges　were　prepared　and　their　water-solubility　as　well　as　logP　values　were　predicted.　Their　cytotoxicity　against　PC-3　cells　was　evaluated　by　MTT　assay.　Cell　cycle　analysis　and　Annexin　V/PI　dual　staining　were　performed　to　investigate　the　anticancer　mechanism.　Results:　The　water-solubility　of　UA　was　enhanced　via　the　chemical　modification.　The　derivatives　bearing　negative　charge　had　weaker　cytotoxic　effects　than　UA　upon　PC-3　cells.　However,　the　ones　bearing　positive　charge　exhibited　more　powerful　cytotoxicity　than　UA　against　the　same　cell　line,　involving　the　occurrence　of　apoptosis　as　well　as　cell　cycle　arrest.　In　particular,　both　elevated　water-solubility　(>70-fold　of　that　of　UA)　and　a　IC50　(48　h)　less　than　10　μmol　·L-1　against　PC-3　cells　were　achieved　by　three　UA　derivatives:　UA-3,　UA-4　and　UA-5b.　The　cell-cycle　arrest　in　G0/G1　as　well　as　apoptosis　(>50%)　was　observed　after　the　treatment　of　one　of　the　three　derivatives　against　PC-3　cells.　Conclusion:　The　introduction　of　groups　of　positive　charge　to　UA　is　an　effective　way　to　improve　its　water-solubility　and　anti-proliferative　activities.