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A liver cyst is hepatic fluid-filled cavities often detected in clinical surveillances such as a health examination. Although the liver cyst is usually asymptomatic and observed without any therapeutic intervention, it can be symptomatic and needs treatment due to its enlargement, hemorrhage, and infection. A 74-year-old woman presented with upper abdominal pain and a huge liver cyst in the left lobe. Several examinations including image findings revealed that the symptom could be derived from the liver cyst. Although there is no definite guideline of treatment for symptomatic liver cysts, percutaneous ultrasound-guided drainage with sclerotherapy or surgery is often selected. Because of anatomical accessibility to the liver cyst and the patient’s wish, we performed endoscopic transgastric drainage with insertion of both an internal stent and an external nasocystic tube. Sclerotherapy with minocycline hydrochloride was performed through the nasocystic tube, and the liver cyst shrunk completely without any complications. This is the first reported method of administering minocycline hydrochloride through a nasocystic tube, which can be a therapeutic option for patients with symptomatic liver cysts.