Objective To investigate the prognostic value of peripheral blood heparin binding protein (HBP) and Toll like receptor 7 (TLR7) combined with lactate/albumin ratio (Lac/Ab) in patients with severe pneumonia and septic shock. Methods A total of 139 patients with severe pneumonia and septic shock admitted to Hebei Chest Hospital from January 2023 to December 2024 were collected. According to the 28-day prognosis, they were divided into the death group (n=48) and the survival group (n=91). The changes in HBP, TLR7, and Lac/Ab levels were compared between the two groups. The correlation of HBP, TLR7, and Lac/Ab was analyzed. ROC curves were used to evaluate the predictive value of HBP, TLR7, and Lac/Ab for mortality in patients with severe pneumonia and septic shock.Results HBP, TLR7, and Lac/Ab levels in the death group on day 1, day 3 and day 7 after admission were higher than those in the survival group (P<0.05). Moreover, HBP, TLR7, and Lac/Ab levels in the survival group on day 3 after admission were lower than those on day 1 after admission (P<0.05). HBP, TLR7, and Lac/Ab were positively correlated in patients with severe pneumonia and septic shock (P<0.05). Multivariate logistic regression analysis showed that baseline APACHE Ⅱ score, baseline SOFA score, day 1 HBP, day 1 TLR7, and day 1 Lac/Ab were independent influencing factors for mortality in patients with severe pneumonia complicated with septic shock (P<0.05). The sensitivity and specificity of the combination of HBP, TLR7, and Lac/Alb for predicting mortality in patients with severe pneumonia and septic shock were 81.25% and 84.62%, respectively. The predictive value was higher than that of HBP, TLR7, or Lac/Alb (P<0.05).Conclusion Using peripheral blood HBP, TLR7, and Lac/Ab in combination to predict mortality in patients with severe pneumonia and septic shock can achieve high sensitivity and specificity, exhibiting good prognostic value