Hepatic cysts are not rare but usually are asymptomatic; however, large ones sometimes show clinical manifestations. Treatment of a solitary hepatic cyst by one-shot instillation of minocycline chloride is reported here; 500 mg of minocycline chloride was instilled into the hepatic cyst, 11 cm in diameter, through a percutaneous transhepatic cholangiography needle under ultrasound guidance. After 5 weeks, the cyst had decreased in size to 5 cm. Five months later, the cyst could not be detected by diagnostic imaging. Fifteen months after the treatment, no reaccumulated fluid was observed. Ultrasound-guided percutaneous one-shot instillation of minocycline chloride seems to be a safe, easy, and useful procedure for treating a hepatic cyst.