We synthesized hinokitiol-modified SN-38 prodrugs and fabricated their nano-prodrugs which are nanoparticles composed of only prodrug molecules by the reprecipitation method. These nano-prodrugs possessed high dispersion stability, and further research revealed that the tropone skeleton of hinokitiol is the key structure for the dispersion stability in our prodrug design. In addition, the nanoparticles of hinokitiol-modified SN-38 showed much higher cytotoxicity against cancer cells than irinotecan, the pharmaceutically available prodrug of SN-38.