Objective To evaluate serum HMGB1 level in the patients with severe acute pancreatitis (SAP) and the effect of pulse high-volume hemofiltration (PHVHF) on the SAP patients. Methods Baseline data were collected from 42 patients with SAP. Among them, 39 patients were divided into two groups: PHVHF group (19 cases) and continuous venovenous hemofiltration (CVVH) group (20 cases). In the PHVHF group, PHVHF was performed using a UF rate of 85 ml/kg per hour for 6-8 h a day followed by standard CVVH (UF rate of 35 ml/kg per hour) for 18 h. In the CVVH group, CVVH was performed using a rate of 35 ml/kg per hour for 24 h. The levels of HMGB1, CRP, TNF-α, endothelin (ET) and APACHE-II score were evaluated at 0, 24, 48 and 72 h. Results The levels of serum ET, CRP, TNF-α and HMGB1 in the patients with SAP were significantly higher than those in the health controls. Using Pearson correlation analysis, HMGB1 was positively correlated with ET (r = 0.912, P < 0.05), CRP (r = 0.678, P < 0.05) and TNF-α (r = 0.906, P < 0.05), but not correlated with APACHE-II (r = 0.287, P > 0.05). The levels of HMGB1, CRP and APACHE-II score decreased (P < 0.05) more significantly 24, 48 and 72 h after hemofiltration than before hemofiltration in the PHVHF and CVVH groups (P < 0.05). There were significant differences in the levels of HMGB1, TNF-α and ET 48 h after hemofiltration between the PHVHF group and the CVVH group (P < 0.05). There were significant differences in the CRP level and APACHE-II score 72 h after hemofiltration between the PHVHF group and the CVVH group (P < 0.05). Conclusions HMGB1 is elevated in the patients with severe acute pancreatitis and positively correlated with ET, CRP and TNF-α. PHVHF is more effective than CVVH in reducing serum HMGB1 and CRP levels and APACHE-II score.