The aim of this study was to explore the therapeutic effects of Continuous High-Volume Hemofiltration (CHVHF) in treating sepsis combined with Multiple Organ Dysfunction Syndrome (MODS). A total of 100 patients with sepsis induced by various causes in combination with MODS (S-MODS) and who were treated in the Department of Critical Care Medicine of our hospital from March 2013 to December 2015 were selected and randomly divided into group A (n=53, for CHVHF) or group B (n=47, for common volume hemofiltration, CVHF). The post-treatment changes of observation indexes were then compared and analysed. Patients in group A exhibited an improvement in body temperature and heart rate (P<0.01), while their Color Index (CI), Mean Artery Pressure (MAP), Systemic Vascular Resistance Index (SVRI), and Stroke Volume Index (SVI) all tended to be stable (P<0.01). Meanwhile, their MODS scores and APACHEII scores decreased significantly (P<0.01), and their Procalcitonin (PCT) and Arterial Blood Lactate level (ABL) improved after treatment. Therefore, CHVHF can stabilize the vital signs and hemodynamics of S-MODS patients as well as improve their tissue perfusion and restore organ functions.