Object To evaluate clinical effect and safety of neutral resin hemoperfusion combined with continuous hemofiltration for the treatment of septic patients with acute kidney injury (AKI). Method A total of 78 cases were enrolled in this study and were assigned into two groups. In group L (n=32), patients received hemoperfusion (HP) and then hemofiltration. In group S (n=46), patients were treated with hemofiltration. A HP session lasted for 2.5 hours, and HP carried out twice every 24 hours. APCHEⅡ score, PO2/FiO2 (OI), mean arterial pressure (MAP), dopamine dose (DA), serum creatinine (Scr), C-reactive protein (CRP), serum IL-6 and IL-10, hemoglobin (Hb) and platelet (Plt) were measured during the treatment. Result HP was well tolerated without any complication in group L. After the initiation of the treatment for 24h, 48h and 72h, APACHEⅡ score, OI, MAP, DA, Scr, CRP and IL-6 improved significantly than before treatment in the two groups (P＜0.05), but without significant changes in serum IL-10, Hb and Plt. In group L, APCHEⅡ score, OI, MAP, DA, IL-6, CRP and Scr improved better than in group S (P＜0.05). No significant differences in serum IL-10, Hb and Plt were detected between the 2 groups after the treatment. Conclusion Neutral resin hemoperfusion combined with continuous hemofiltration can improve APACHEⅡ score, PO2/FiO2 and MAP, reduce serum levels of CRP, creatinine and IL-6, but had no effects on serum IL-10, hemoglobin and platelet in septic patients with AKI