Objective To explore the evaluation value of heparin-binding protein combined with serum procalcitonin (PCT) and C-reactive protein (CRP) in disease severity and prognosis of elderly emergency patients with sepsis. Methods A total of 82 elderly emergency patients with sepsis confirmed in the hospital were retrospectively enrolled as study group from June 2022 to February 2024. According to disease severity, they were divided into sepsis group (n=52) and septic shock group (n=30), levels of serum heparin-binding protein, PCT and CRP were compared between the two groups within 24h after admission. The correlation of the three indexes was analyzed. The scores of acute physiological and chronic health evaluation Ⅱ (APACHE Ⅱ) within 24h after admission and 28d prognosis were statistically analyzed. The correlation between serum heparin-binding protein, PCT, CRP levels and APACHE Ⅱ score was analyzed, and predictive value of the above indexes for prognosis was evaluated by receiver operating characteristics (ROC) curves. Results The levels of heparin-binding protein, PCT and CRP in septic shock group were higher than those in sepsis group (P<0.05). The levels of serum heparin-binding protein, PCT and CRP were positively correlated with disease severity in elderly patients with sepsis (P<0.05). Within 28d after admission, there were 71 survival cases (survival group) and 11 death cases (death group), respectively. The levels of serum heparin-binding protein, PCT and CRP, and APACHE Ⅱ score in survival group were lower than those in death group (P<0.05). The levels of serum heparin-binding protein, PCT and CRP were positively correlated with APACHE Ⅱ score in elderly patients with sepsis (P<0.05). ROC curves analysis showed that area under ROC curve (AUC) values of serum heparin-binding protein, PCT, CRP and combined detection for predicting prognosis were 0.768, 0.764, 0.748 and 0.818, respectively. The sensitivity and specificity of combined detection were 81.82% and 88.73%, showing high predictive efficiency (P<0.05). Conclusion The levels of serum heparin-binding protein, PCT and CRP are positively correlated with disease severity in elderly patients with sepsis, and combined detection of the three indexes has high predictive efficiency for prognosis of elderly emergency patients with sepsis