['Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal condition in children with Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM). This study aimed to identify commonly available clinical and laboratory predictors that might help clinicians decide to perform the bone marrow and immunological tests for HLH in paediatric EBV-associated IM.', 'A retrospective case-control study of patients aged <18 yr diagnosed with EBV-associated IM and HLH from 1991 to 2010 in a tertiary medical centre was conducted. A diagnosis of HLH was defined as fulfilling the criteria of the guidelines of the HLH-2004 protocol of the Histiocyte Society and consisted of at least evidence of hemophagocytosis in a bone marrow biopsy.', 'A total of 177 IM and 27 HLH patients were enrolled. The mean age was 5.3 yr with a female-to-male ratio of 1.06. The most common characteristics (>70% of patients) were fever, lymphadenopathy and hepatomegaly. In addition to the diagnostic criteria of HLH including fever, splenomegaly, cytopenia, hyperferritinaemia, hypertriglyceridemia and/or hypofibrinogenaemia, children with HLH had a significantly higher rate of prolonged fever >10 d, hepatomegaly, jaundice, general malaise, elevated aspartate aminotransferase, lactate dehydrogenase, C-reactive protein and hypoalbuminaemia compared to those with IM (all P < 0.01). Multiple logistic regression confirmed that hypoalbuminaemia (OR = 23.1, P = 0.01) was an independent predictor of paediatric HLH, with a high sensitivity (96%) and a good negative likelihood ratio (0.06) in patients with EBV-associated IM.'] Is hypoalbuminaemia an independent predictor for hemophagocytic lymphohistiocytosis in childhood Epstein-Barr virus-associated infectious mononucleosis?