Objective: To establish a prediction Nomogram based on prognostic factors for children with hemophagocytic lymphohistiocytosis (HLH). Methods: A retrospective analysis of pediatric HLH cases diagnosed at the Affiliated Hospital of Zunyi Medical University between January 2012 and December 2022 was conducted. Cox regression analysis was used to identify prognostic factors for pediatric HLH patients. The C-index, ROC curve, and AUC were used to evaluate the discrimination of the model. The DCA was used to evaluate the clinical application value of the model. Results: A total of 133 cases of secondary pediatric HLH patients were included in this study, with 45 deaths and 88 survivors. Univariate analysis showed that age ≤ 2 years, PLT ≤ 50×10 ⁹/L, HB ≤90 g/L, AST ≥ 200 U/L, CK-MB ≥ 50 U/L, LDH ≥ 1000 U/L, SF ≥1500 μg/L, PT ≥ 20 s, APTT ≥ 40 s, hypoalbuminemia, hypofibrinogenemia, mechanical ventilation, splenomegaly, ARDS, respiratory failure,CNSL, shock, DIC, pulmonary hemorrhage, and gastrointestinal bleeding are risk factors for the survival of those secondary pediatric HLH patients ( P <0.05), while blood purification therapy may be a protective factor for HLH prognosis ( P = 0.049). Multivariable Cox showed that CNSL (HR = 3.18, 95%CI = 1.72-5.89), PLT ≤ 50×10^9/L (HR = 2.16, 95%CI = 1.11-4.19), hypoalbuminemia (HR=2.65, 95%CI=1.14-5.17), and hypofibrinogenemia (HR = 2.48, 95%CI = 1.19-5.14) were independent risk factors for the outcome of children with HLH, while the use of blood purification therapy (HR = 0.32, 95%CI = 0.16-0.64) was an independent protective factor. A Nomogram prediction model was constructed using R software, and the ROC curve , C-index, and calibration curve showed good discrimination and fit of the model. The DCA curve showed that the model had good clinical applicability. Finally, based on the Nomogram score and HR value, the subjects were divided into three groups, and it was found that the mortality rate in the high-risk group was significantly higher than that in the low-risk group. Conclusion: The development of a Nomogram to predict the prognosis of secondary pediatric HLH patients has good discrimination and accuracy and may have good clinical application value.