Abstract： Fever of unknown origin （FUO） is challenging to diagnose due to its obscure etiology， which often renders various treatment modalities ineffective. This paper proposes a method that integrates modern medical diagnostic techniques with the Chinese medicine theory of "symptom clusters" for syndrome differentiation. Physicians can categorize the relevant symptoms of FUO patients into "symptom clusters" and conduct a comprehensive study based on the "pathogenesis – symptom" cluster combinations. Eventually， they can incorporate these symptoms into the corresponding Chinese medicine syndromes for syndrome differentiation and treatment. This approach aims to improve the current clinical diagnosis and treatment of FUO and timely integrate Chinese medicine therapies into the treatment process. It can effectively avoid the risks associated with potential diseases in FUO，promptly intervene in the spectrum of FUO symptoms，reduce the misdiagnosis rate of FUO，and also improve the adverse prognosis caused by the misuse of medications.