Hemophagocytic syndrome (HPS) is a severe, potentially life-threatening disorder characterized by an excessive activation of macrophages, such as may occur in the setting of lupus. A 62-year-old Japanese woman treated with etanercept for rheumatoid arthritis developed persistent fever, cytopenia, coagulopathy, and hyperferritinemia. Simultaneously, lupus-like features including pleuritis, hypocomplementemia, and positive autoantibodies were observed. She was diagnosed with HPS related to etanercept-induced lupus, and underwent immunosuppressive therapy with successful recovery. To our knowledge, this is the first case of etanercept-induced lupus accompanied by HPS. This case suggests that HPS should be considered as a complication during TNF-α inhibitor therapy.