We present a successfully treated case of a multi-septated massive hepatic cyst with repeated injection of minocycline hydrochloride (MINO). A 57-year-old Japanese female complaining of right back pain, hypochondralgia and hypertension had a multi-septated massive hepatic cyst, 25 cm in diameter. Multiple cysts of various sizes were also seen in liver and kidneys. In order to reduce the size of the massive hepatic cyst to relieve the complaints, we performed the reduction therapy of the cyst. After a pig tail catheter was inserted into the cyst, the cystic fluid was aspirated and then a total of 3900 mg of MINO was injected. Red-brownish, serous cystic fluids were obtained. Cytology and bacterial culture were negative, but the LDH (3, 336 IU/l) and CA19-9 (751,500 U/l) concentrations were very high. After the 9 series of the therapy, the cyst was minified on CT and the patient's symptoms were relieved. Furthermore high blood pressure was improved. Thus, the therapy of size-reduction for a massive hepatic cyst is revealed to be very safe and useful.