〔Abstract〕 Objective To investigate the effect of hemoperfusion (HP) combined with continuous veno-venous hemofiltration (CVVH) in patients with acute severe organophosphorus poisoning. Methods A total of 90 patients with acute organophosphorus poisoning admitted to Fujian Provincial Hospital from May 2018 to June 2021 were selected and divided into a control group and an observation group by random number table method, with 45 cases in each group. The control group was treated with pentadiol, fluoxidine iodide, mechanical ventilation, HP, etc. The observation group was treated with CVVH in addition to the control group, and the therapeutic effects of the two groups were compared. Results The coma time, mechanical ventilation time and hospitalization time in the observation group were shorter than those in the control group, and the differences were statistically significant (P < 0.05). After 24 h of treatment, the lactate of the observation group was lower than that of the control group, and the cholinesterase was higher than that of the control group, with statistical significances (P < 0.05). After 24 h of treatment, the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the observation group were lower than those in the control group, the differences were statistically significant (P < 0.05). The incidence of complications in the observation group was lower than that in the control group during treatment, the difference was statistically significant (P < 0.05). Conclusion HP combined with CVVH has a better therapeutic effect on patients with acute severe organophosphorus poisoning, which can effectively correct the internal environment disorder, reduce the inflammatory response of the body and reduce the incidence of complications.