Background: Juvenile xanthogranuloma (JXG) is a rare non-Langerhans cell histiocytosis that typically presents as self-limiting cutaneous lesions in infants and young children. However, systemic involvement can lead to severe organ dysfunction and poses significant therapeutic challenges. Case presentation: We report a case of chemotherapy-refractory, multisystem JXG harboring BRAF V600E mutation in a 28-month-old male. The patient presented with recurrent fever, bilateral orbital involvement, and progressive multisystem infiltration without cutaneous lesions. First-line chemotherapy failed to control disease progression and was complicated by pulmonary infection. Oral dabrafenib monotherapy induced rapid clinical and radiologic remission, with clearance of BRAF V600E in peripheral blood cell-free DNA . The patient has maintained remission for four years, including two years off-therapy. Conclusion: This case demonstrates durable remission with dabrafenib in BRAF-mutant systemic JXG and highlights the potential of BRAF-targeted therapy as an effective and safer alternative to conventional chemotherapy in refractory cases.