Blastocystis hominis is a unicellular parasitic microorganism commonly found in the gastrointestinal tracts of humans. Its pathogenicity remains uncertain. A 78-year-old female patient with renal cell carcinoma and lung metastasis complained of right upper quadrant pain. Abdominal ultrasonography and computed tomography scan showed a huge liver cyst in which a plethora of Blastocystis hominis was identified through cyst fluid analysis. The patient then received her first course of metronidazole treatment for 14 days. One year later, she underwent resection of the liver cyst due to internal bleeding and subphrenic hematoma induced by cyst drainage procedure. Cyst fluid analysis again revealed a profusion of Blastocystis hominis. Stool examination showed a negative result 45 days after a course of metronidazole for 20 days. To the best of our knowledge, this is the first case of the presence of Blastocystis hominis in liver cyst. However, further studies are required to determine the adequate course of antibiotic treatment and necessity of drainage or resection of the infected liver cyst.