Objective To investigate the changes of serum human kallikrein-binding protein (Kallistatin, Kal) and vascular endothelial cadherin (VE-cad) in patients with septic shock and their relationship with prognosis.Methods A total of 252 patients with septic shock admitted to the Department of Critical Care Medicine, Hangzhou Hospital of Traditional Chinese Medicine, from March 2016 to March 2018, were prospective selected. 74 patients were excluded according to pre-specified exclusion criteria, and there were 178 patients with septic shock who were eventually included in the study. According to the 28-day prognosis, they were divided into survival group (120 cases) and death group (58 cases). The changes of serum Kal and VE-cad levels on the 1, 3 and 5 days of ICU were observed. The acute physiology and chronic health status scoring system II (APACHE II) score and sequential organ failure assessment (SOFA) score of sepsis patients were recorded. Pearson correlation analysis was used to analyze the correlation of serum Kal and VE-cad with APACHE II score and SOFA score. Evaluation of prognostic value of serum Kal and VE-cad in patients with septic shock was performed with the receiver operating characteristic curve (ROC). Binary logistic regression was used to analyze the influence factors for septic shock death.Results The oxygenation index and serum albumin (ALB) levels in the death group of patients with septic shock were lower than those in the survival group (P < 0.05). Mechanical ventilation time, ICU hospitalization days were longer than those in the survival group (P < 0.05), the levels of serum C-reactive protein (CRP), procalcitonin (PCT), extravascular lung water index (EVLWI), APACHE II score, and SOFA score were higher than those in the survival group (P < 0.05). The serum Kal and VE-cad levels of the death group and the survival group were different at different time points (P < 0.05); the serum Kal and VE-cad levels of the death group and the survival group were different (P < 0.05); the change trend of serum Kal and VE-cad levels of the death group and the survival group were different (P < 0.05), and the serum Kal level in the death group of patients with septic shock (1, 3 and 5d of ICU admission) were lower than those in the survival group (P <0.05). Serum VE-cad level in the death group (1, 3 and 5d of ICU admission) were higher than those in the survival group (P <0.05). There was a negative correlation between serum Kal level and APACHE II score and SOFA score (r = -0.397 and -0.466, both P < 0.05). Serum VE-cad was positively correlated with APACHE II score and SOFA score (r = 0.173 and 0.192, both P < 0.05). Within 24h of admission, the area under curve (AUC) of serum Kal, VE-cad and their combined detection were 0.687 (95% CI: 0.604, 0.770), 0.859 (95% CI: 0.805, 0.912), and 0.890 (95% CI: 0.845, 0.936), respectively; the sensitivity and specificity of serum Kal were 81.0% (95% CI: 77.2%, 85.4%) and 50.0% (95% CI: 47.4%, 53.1%); the sensitivity and specificity of VE-cad were 69.0% (95% CI: 64.9%, 72.6%) and 86.7% (95% CI: 82.2%, 91.4%); the sensitivity and specificity of combined method to predict the death of septic shock patients was 82.2% (95% CI: 78.1%, 86.8%) and 89.6% (95% CI: 85.2%, 95.4%). CRP [R = 1.221, (95% CI: 1.022, 1.459)], PCT [R = 1.195, (95% CI: 1.035, 1.380)], VE-cad [R = 1.373, (95% CI: 1.055, 1.787)], and EVLWI [R = 1.846, (95% CI: 1.178, 2.893)] were risk factors for death in patients with septic shock (P < 0.05); Kal [R = 0.428, (95% CI: 0.190, 0.966)] was protective factor for death in patients with septic shock (P < 0.05).Conclusion CRP, PCT, VE-cad, Kal, and EVLWI were influence factors for death in patients with septic shock. The serum VE-cad level increased and Kal decreased in patients with septic shock. The combined detection of VE-cad and Kal has certain clinical value in evaluating the prognosis of patients with septic shock.