China has the second highest incidence rate of TB infections in the world. Therefore, the Chinese government has instituted specific health policies and created specialized TB hospitals to treat confirmed patients with TB. However, TB is known as “a great mimicker” due to its diverse range of clinical manifestations, which make early diagnosis difficult and may even result in misdiagnosis. In large first-class hospitals in China, TB patients are admitted to the hospital mostly due to FUO, and after undergoing abundant and differential diagnosis, they are finally diagnosed with TB. Therefore, the diagnosis of TB that presents as FUO is quite difficult. According to clinical data published by our hospital, TB infection ranks first in the discharge diagnoses of patients admitted with FUO. Meanwhile, in recent years, a growing number of patients have been infected with drug-resistant TB, refractory TB, and severe TB; these patients have to seek medical care in large general hospitals because of difficulties in diagnosis and treatment. TB-HLH is a type of severe TB. Our retrospective case analysis has demonstrated that all TB-HLH patients in our study were admitted to the hospital with FUO, which is undoubtedly a challenge for clinicians. TB-HLH was first reported in the 1980s, and there has been a growing amount of literature on TB-HLH in recent years. Nevertheless, these reports both from China and abroad, are single case reports. The current report is the largest single-center case summary in the world thus far.