We herein report the case of a patient with intestinal gastrointestinal stromal tumor(GIST) who was refractory to molecular targeted therapy but showed improvement in quality of life(QOL) after palliative surgery. A 60-year-old man with a high-risk diagnosis underwent an incomplete resection for multiple abdominal tumors. He was treated with molecular targeted therapy after the operation, but he acquired secondary resistance to imatinib and intolerance to sunitinib. Although the patient was treated with imatinib again, he experienced vomiting, abdominal pain, and leg edema because of tumor regrowth 7 months after the re-treatment. His general condition deteriorated, and his Eastern Cooperative Oncology Group (ECOG) performance status(PS) was 3. After 35 months of the first treatment, palliative resection of tumors was performed to control the symptoms. After the operation, the general condition of the patient improved, and his ECOG PS was maintained as 1 for at least 4 months. Palliative resection may improve QOL.