This study aims to investigate the effects of continuous renal replacement therapy (CRRT) combined with ulinastatin on cytokine levels and prognosis in patients with sepsis. The control and study groups (40 cases each) were established. The control group received CRRT alone, while the study group received CRRT plus ulinastatin treatment, with both groups being treated for 7 days. We compared the following parameters before and after treatment between the two groups: Sequential Organ Failure Assessment (SOFA) scores, Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, renal function indicators [cystatin C (CysC), blood urea nitrogen (BUN), and serum creatinine (SCr)], inflammatory factors [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and procalcitonin (PCT)], and immune function parameters (CD4+, CD8+, CD4+/CD8+ ratio). Additionally, we recorded adverse reactions and 28-day mortality rates in both groups. After 7 days of treatment, the study group showed significantly lower SOFA scores, APACHE II scores, serum levels of CysC, BUN, Scr, TNF-α, CRP, PCT, and peripheral blood CD8+ compared to the control group, while demonstrating higher peripheral blood CD4+ and CD4+/CD8+ ratio. During the treatment period, there was no significant difference in the incidence of adverse reactions between the two groups. However, the 28-day mortality rate was significantly lower in the study group compared to the control group. For patients with sepsis, the combination of CRRT and ulinastatin therapy can significantly improve disease severity, inflammatory factors, renal function, and immune function, while reducing mortality rate.