We report a case of Stauffer syndrome-like findings in a patient with metastatic renal carcinoma treated by surgery and molecular targeted therapy. The patient was a 58-year-old woman diagnosed with renal carcinoma with multiple metastases. She had hepatosplenomegaly and hepatic dysfunction with elevated serum liver enzyme and IL-6 levels. Treatment with temsirolimus and axitinib reduced the size of the local and metastatic tumors and simultaneously improved the hepatosplenomegaly. The local tumor was excised by laparoscopic nephrectomy, treated with axitinib and then with nivolumab. With the reduction in the metastatic tumor size, serum liver enzyme and IL-6 levels decreased. It was suggested that molecular targeted therapy is an effective treatment when the findings of metastatic renal cell carcinoma, are similar to those of Stauffer syndrome.