To explore the clinical correlation and prognostic value of the Albumin-Bilirubin (ALBI) score in children with secondary hemophagocytic syndrome(sHLH). A retrospective analysis was conducted on the data of children's sHLH cases clearly diagnosed in the Affiliated Hospital of Zunyi Medical University from January 2012 to March 2023. Survival analysis was conducted according to the ALBI classification. Spearman correlation analysis was conducted between the ALBI score and clinical indicators. The Receiver Operating Characteristic(ROC) curve was used to evaluate the ALBI score, select the best cutoff value, and evaluate the accuracy of prognostic prediction value. Kaplan-Meier method was used to draw the survival curve. Log-rank method was used to compare the differences of survival curve between groups. Cox regression was used for prognostic analysis and restricted cubic spline curves used to calculate the relationship between ALBI scores and the risk of death in children with sHLH. A total of 128 children with sHLH were included in this study, with a median age of 38(13.25, 84) months. There were 70 males (54.69%) and 58 females (45.31%). The survival analysis results of ALBI grading showed that the survival rate of HLH patients with ALBI grade 3 was significantly lower than those with ALBI grades 1 and 2. Spearman correlation analysis results showed that ALBI score was positively correlated with splenomegaly, respiratory failure, disseminated intravascular coagulation(DIC), pulmonary hemorrhage, gastrointestinal hemorrhage, central nervous system involvement, ALT, AST, TG, LDH, PT, APTT, and SF (the correlation coefficients are: r =0.181, 0.362, 0.332, 0.221, 0.351, 0.347, 0.391, 0.563, 0.180, 0.448, 0.483, 0.37, 0.356), and was negatively correlated with HB, PLT, and FIB (the correlation coefficients are: r =-0.321, -0.316, -0.423), but was not significantly correlated with EBV infection, fungal infection, hepatomegaly, and ANC (P >0.05). Using the ROC curve, the cutoff value of ALBI was -1.76. Single factor Cox regression analysis results showed that HB< 90 g/L, ALT≥80 U/L, AST≥200 U/L, LDH≥1 000 U/L, PT≥20 s, APTT≥40 s, FIB< 1.5 g/L, ALBI≥-1.76, combined pulmonary hemorrhage, DIC, central nervous system involvement, gastrointestinal bleeding, and not using blood purification may be the prognostic risk factors for children with sHLH (P < 0.05). Multivariate Cox regression results showed that FIB< 1.5 g/L (HR =2.119, 95% CI :1.028-4.368), ALBI≥-1.76 (HR =2.452, 95%CI :1.233-4.875), and central nervous system involvement (HR=4.674, 95%CI :2.486-8.789) were independent risk factors affecting prognosis, while blood purification (HR =0.306, 95%CI :0.153-0.612) was an independent protective factor for prognosis. The application of restricted cubic splines shows that the risk of death increases with the increase of ALBI score. The area under the ROC curve (AUC) of the ALBI score for predicting the risk of 1-week, 2-week, 4-week, and overall mortality were 0.825, 0.807, 0.700, and 0.693, respectively, indicating good predictive performance for early mortality risk. According to subgroup analysis results of clinical manifestations, compared with the ALBI < -1.76 group, ALBI≥-1.76 was associated with age ≤2 years, EBV infection, HLH-1994/2004 treatment, concomitant respiratory failure, and ANC≤1.0×10 9/L, HB< 90 g/L, PLT < 100×109/L, TG≥3.0 mmol/L, LDH≥1 000 U/L, APTT≥40 s, and FIB< 1.5 g/L (P < 0.05). The ALBI score is related to the clinical characteristics and laboratory indicators of sHLH, and can be used as a beneficial indicator for assessing the prognostic risk of sHLH in children. It has good accuracy and clinical application value in predicting the prognosis of sHLH in children.