Abstract: Objective To compare the clinical efficacy of hemoperfusion (HP) times in patients with severe acute organophosphorus poisoning. Methods Eighty-six patients with severe acute organophosphorus poisoning (AOPP) admitted to intensive care unit from January 2014 to July 2018 were divided into 3 groups basing on times of hemoperfusion (HP), including a HP0 group of 26 cases received no hemoperfusion treatment, a HP1 group of 31 cases received once hemoperfusion treatment, and a HP2 of 29 cases received twice or more hemoperfusion treatments. Then the total dose of atropine and pralidoxime, recovery of 80% serum cholinesterase activity, duration of coma, hospital stay, time of mechanical ventilation, acute physiology and chronic health status scoring system Ⅱ (APACHE Ⅱ) score at 72 h after admission, and incidence of complications (intermediate syndrome, poisoning rebound, arrhythmia, organ dysfunction syndrome) and mortality of the 3 groups were compared. Results Hemoperfusion treatment was correlated with total dose of atropine and pralidoxime, recovery of 80% serum cholinesterase activity, duration of coma, hospital stay, time of mechanical ventilation, acute physiology and chronic health status scoring system Ⅱ (APACHE Ⅱ) score at 72 h after admission, the incidence of complications (intermediate syndrome, poisoning rebound, organ dysfunction syndrome) in HP2 was less than the others and mortality (P<0.05 for all), the incidence of arrhythmia in HP1 and HP2 was less than the HP0. Conclusion Multiple times of hemoperfusion is a supplement to conventional treatment showed significant efficacy for AOPP patients.