Objective: The purpose of this study is to investigate the clinical efficacy of the combination therapy of sorafenib and DOAP (doxorubicin, vincristine, cytarabine, and prednisone) in the treatment of a case of Langerhans cell sarcoma (LCS) negative for BRAF V600E mutation. Furthermore, we aim to retrospectively analyze the clinical characteristics, diagnosis, treatment, and prognosis of LCS. Methods: We conducted a retrospective analysis of the clinical data, pathological examination, and treatment of a patient with LCS, along with a review of relevant literature both domestic and international. Results: After four cycles of sorafenib combined with DOAP chemotherapy, the patient underwent sequential local radiotherapy, resulting in complete remission of the disease. The treatment-related side effects were manageable, and the patient tolerated the treatment well. The patient has survived for 40 months. Conclusion: LCS is a highly rare and aggressive malignancy that can involve various organs throughout the body. It presents with complex and diverse clinical manifestations, progresses rapidly, and has a poor prognosis. Treatment options include surgery, radiotherapy, chemotherapy, targeted therapy, and hematopoietic stem cell transplantation. However, there is currently no universally recognized optimal treatment protocol, and personalized treatment is necessary. Targeted therapy offers new hope for LCS patients.