Objective To investigate the relationship between the clinical invasive interventions during hospitalization and the admission indicators within 24 hours with death within 28-day after admission in sepsis patients. Methods The clinical data of 112 sepsis patients who were admitted to the First Medical Center of Chinese PLA General Hospital from Jan. 2016 to Dec. 2018 were analyzed retrospectively. Four clinical invasive interventions (mechanical ventilation, tracheal intubation, continuous renal replacement therapy[CRRT] and deep vein catheterization) and admission indicators (including demographic characteristics, vital signs and laboratory indexes) that may have an impact on the death of sepsis patients were selected during hospitalization, and the 28-day survival of patients was taken as the outcome variable. The above parameters were compared between the survival group (n=81) and the death group (n=31), and the independent risk factors of sepsis death within 28-day after admission were determined by multivariate logistic regression analysis. Results There were statistically significant differences in age, the sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluationⅡ (APACHEⅡ) score, IL-6, procalcitonin, aspartate aminotransferase, CRRT and deep vein catheterization between the two groups (all P<0.05). The results of the multivariate logistic regression analysis revealed that high IL-6 level (odds ratio[OR]=1.001, P=0.011), low procalcitonin level (OR=0.966, P=0.005) and CRRT (OR=6.846, P=0.002) were independent risk factors of death within 28-day after admission in sepsis patients. Conclusion Sepsis patients with increased IL-6 level, decreased procalcitonin level and CRRT during hospitalization have a higher risk of death within 28-day after admission. Close observation and dynamic monitoring of changes in IL-6, procalcitonin and renal function will be beneficial for early identification of septic patients who might have adverse clinical outcomes. The proportions of essential invasive interventions such as mechanical ventilation, tracheal intubation, CRRT, and deep venous catheterization are higher in dead patients, so clinicians need to carefully evaluate and accurately grasp the balance point.