Objective To explore the risk factors of hemophagocytic lymphohistiocytosis (HLH) secondary to severe pneumonia in children. Methods The clinical data of children hospitalized from October 1, 2012 to December 31, 2019 and diagnosed with severe pneumonia secondary to HLH (observation group) were retrospectively analyzed. Children with severe pneumonia hospitalized in 2019 were randomly selected as the control group. Clinical characteristics, laboratory tests and treatment results between the two groups were compared, and the predictive value of different indicators for HLH secondary to severe pneumonia were analyzed. Results There were 38 cases in the observation group and 96 cases in the control group. Compared with the control group, the observation group had a higher age of onset, a higher proportion of 6 months to 2 years old, a higher proportion of fever, lethargy, poor reaction and irritability, a longer median heat course, a higher proportion of liver, spleen, lymph node swelling, rash and edema, and a lower proportion of fine wet rales, shortness of breath and / or cyanosis in lung auscultation (all P< 0.05). In the observation group, ALT, AST and LDH were abnormally elevated, the proportion of albumin < 30 g/L, CRP > 8 mg/L, and PCT > 0.15 ng/mL was higher, the proportion of adenovirus and fungi was higher, and the proportion of RNA virus was lower. The difference was statistically significant (P<0.05). The incidence of pleural effusion, lung consolidation/atelectasis and extensive lesions of both lungs in the observation group were higher than that in the control group (all P<0.05), the length of hospitalization was longer than that in the control group, and the mortality and ICU occupancy rate were higher than that in the control group (all P<0.05). Lactate dehydrogenase has a high predictive value for HLH secondary to severe pneumonia. The area under the curve is 0.93 (0.88-0.98), and the cutoff value is 804.35 IU/L. Conclusion Compared with those without HLH, children with HLH secondary to severe pneumonia have older onset age, longer hospitalization time, higher mortality, higher lactate dehydrogenase and lower albumin. Children with severe pneumonia with adenovirus infection and pleural effusion are more likely to develop HLH.