Background. The mortality risks for secondary hemophagocytic lymphohistiocytosis in the induction stage and investigated prognostic factors need to be further discussed. Objective. The aim of this study is to establish a clinical model for predicting early death in adult patients with secondary hemophagocytic lymphohistiocytosis. Design, Participants, and Main Measures. The baseline characteristics, laboratory examination results, and 8-week survival rate of 139 adult sHLH patients diagnosed from January 2018 to December 2018 were analyzed retrospectively, and a prognostic model was constructed with low-risk (score 0-2), medium-risk (score 3), and high-risk (score >= 4) as parameters. Key Results. Univariate analysis confirmed that early death was not related to the type of HLH but significantly related to the patient's response to first-line treatment. The peripheral blood cell count was significantly decreased, C-reactive protein was higher, glutamyl transpeptidase and total bilirubin were higher, albumin was significantly lower, urea nitrogen was higher, hypocalcemia and hyponatremia, deep organ hemorrhage and D-dimer increased, cardiac function damage and HLH central involvement, sCD25 increased, and EB virus infection were predictive factors of early death. In the multivariate model, patients' response to first-line treatment was a good predictor of overall survival, and hypocalcemia and deep organ bleeding were associated with poor survival. The risk factors were scored and graded according to the risk ratio. The 8-week overall survival rates of the low-risk group (82 cases), medium-risk group (36 cases), and high-risk group (21 cases) were 85.4%, 52.8%, and 23.8%, respectively (P < 0.001). Conclusions. The early death of sHLH patients is closely related to some laboratory examination results. Attention should be paid to identify high-risk patients, choose effective first-line induction therapy, achieve deep remission as soon as possible, prevent deep organ bleeding, correct electrolyte disorders, and improve the early survival rate of sHLH patients.