Objective ·To study early expression levels of serum heparin-binding protein (HBP) and its potential value in early alarming for prognosis and occurrence of sepsis in patients with severe burns. Methods ·Retrospective analysis was performed on medical records of 52 severely burned patients admitted to the Department of Burn and Plastic, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine during January 2021 to May 2023. General data of patients on gender, age, total burn area, body mass index (BMI), and whether endotracheal intubation or incision was performed were collected. The level of HBP, serum procalcitonin (PCT), serum C-reactive protein (CRP) and the count of white blood cells within 48 h of admission were collected. The scores of acute physiological and chronic health assessment evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) within 48 h of admission were collected. Patients were divided into death group and survival group according to the status at discharge. According to whether sepsis occurred during hospitalization, the patients were divided into sepsis group and non-sepsis group. According to whether shock occurred, the septic patients were divided into sepsis without shock group and septic shock group. Risk factors for death, sepsis, and septic shock in severely burned patients were analyzed by using Logistic regression models. Receiver operator characteristic (ROC) curve analysis was established to study risk factors, which may alarm the occurrence of poor prognosis, sepsis, and septic shock. Results ·Compared with the survival group, patients in the death group were older, and the difference was statistically significant (P=0.036). Differences in burn area and whether tracheal intubation or tracheotomy was performed were statistically significant in patients with or without sepsis (P=0.011, P=0.001). Compared with the survival group, the serum HBP levels were higher in the death group, and the difference was statistically significant (P=0.002). Compared with the non-sepsis group, patients in the sepsis group had higher levels of serum HBP, APACHE Ⅱ scores, and SOFA scores, and the differences were statistically significant (all P<0.05). The differences in other indicators were not statistically significant. Compared with the sepsis without shock group, the septic shock group had higher HBP levels, with a statistically significant difference (P=0.008). Logistic regression analysis showed that HBP was an independent risk factor for death in patients with severe burns during hospitalization and also an independent risk factor for the occurrence of septic shock in patients with sepsis after severe burns. ROC curve analysis showed that the area under the curve (AUC) for HBP in predicting patient mortality during hospitalization was 0.798; when HBP ≥147.03 ng/mL, its sensitivity and specificity were 88.33% and 70.00%, respectively. The AUC for HBP in predicting the occurrence of septic shock in patients with sepsis after severe burns was 0.789; when HBP ≥147.03 ng/mL, its sensitivity and specificity were 90.00% and 63.20%, respectively. Conclusion ·The level of serum HBP within 48 h of admission might be used as an early alarming index for prognosis in patients with severe burns and for the occurrence of septic shock in patients with sepsis following severe burns.