To analyze the critical factors of infection-associated Hemophagocytic lymphohistiocytosis (HLH) in children, so as to provide theoretical basis for clinicians to evaluate the disease condition, formulate treatment plan and improve prognosis. This study is a retrospective analysis. 60 cases of children with infection-associated HLH were divided into critical and non-critical groups based on the presence of multiple organ dysfunction syndrome (MODS), and the clinical characteristics and laboratory data of the two groups of children were analyzed. A multifactor logistic regression analysis model was used to assess the independent risk factors affecting critical illness in children with infection-associated HLH, and the Receiver Operating Characteristic (ROC) curve analysis was used to evaluate the predictive value of risk factors for critical illness in children with infection-associated HLH. Children in the critical group with HLH had a younger age at onset. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), gamma-glutamyl transferase (GGT), D-dimer (DD), and triglycerides (TG) were significantly higher in the critical group, while albumin (ALB) was significantly lower, showing statistical significance (P < 0.05). Multifactorial logistic regression analysis of age, ALB, and TG showed that younger age and lower ALB were associated with a higher risk of MODS in children with infection-associated HLH, with age and ALB being independent risk factors for critical illness. ALB predicted the ROC area under the curve for critical children with infection-associated HLH was 0.765 (95% CI: 0.643-0.888, P = 0.011), with the optimal cut-off value being 32.50 g/L (sensitivity = 68.3%, specificity = 84.2%); age predicted the ROC area under the curve for critical children with infection-associated HLH was 0.711 (95% CI: 0.570-0.851, P = 0.009), with the optimal cut-off value being 1.50 years (sensitivity = 70.7%, specificity = 68.4%). This study suggests that younger patients and those with hypoalbuminemia among infection-related HLH patients are more likely to develop MODS. In the future, verification will be required through large-scale, multi-center studies.