〔Abstract〕 Objective To investigate the effect of continuous veno-venous hemofiltration (CVVH) combined with hemperfusion (HP) in acute severe organophosphorus pesticide poisoning (ASOPP). Methods A total of 74 ASOPP patients admitted to General Hospital of Pingmei Medical Group from August 2020 to July 2021 were selected as the research objects. According to random number table method, they were divided into an observation group and a control group, with 37 cases in each group. The control group was given HP treatment, and the observation group was given CVVH treatment on the basis of the control group. Clinical indicators, inflammatory factors, biochemical indicators, prognosis, incidence of complications and mortality were compared between the two groups. Results Compared with the control group, the duration of coma, cholinesterase (ChE) recovery time, hospital stay in the observation group were significantly shorter, and the dosage of atropine was significantly lower, with statistical significances (P < 0.05). After 7 d of treatment, the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) in the two groups were significantly decreased in the observation group, and were significantly lower than those in the control group, the differences were statistically significant (P < 0.05). After 7 d of treatment, the levels of alanine aminotransferase (ALT), creatine kinase (CK) and creatine kinase isoenzyme (CK-MB) in the two groups were significantly decreased, and the levels of ALT, CK and CK-MB in the observation group were significantly lower than those in the control group, with statistical significances (P < 0.05). After 7 d of treatment, the assessment of acute physiology and acute physiology chronichealth evaluation scoring system Ⅱ (APACHE Ⅱ) and the sequential organ failure assessment score (SOFA) were significantly decreased, and the scores of APACHE Ⅱ and SOFA in the observation group were significantly lower than those in the control group, with statistical significances (P < 0.05). The incidence of complications and mortality in the observation group were significantly lower than those in the control group, with statistical significances (P < 0.05). Conclusion Compared with pure HP treatment, CVVH combined with HP treatment in ASOPP patients can more effectively improve the clinical indicators, regulate the levels of inflammatory factors and biochemical indicators, improve the prognosis, and reduce the incidence of complications and mortality.