Objective? To explore the effects of sequential blood purification on levels of serum cholinesterase (CHE), neuron specific enolase (NSE), creatine kinase (CK), lactate dehydrogenase (LDH), creatine kinase MB isoenzyme (CK-MB) and ischemia modified albumin (IMA) in patients with acute severe organophosphorus poisoning. Methods? 80 patients with acute severe organophosphorus poisoning treated in Qingyang Second People's Hospital from December 2019 to November 2021 were divided into the control group (40 cases) and the observation group (40 cases) by random number table method. Routine emergency treatment was given to all patients, patients in the control group were treated with hemoperfusion on this basis, patients in the observation group were treated with sequential blood purification on the basis of the control group, patients in both groups were observed until discharge. The clinical efficacy, clinical indexes after treatment, levels of serum CHE, NSE and myocardial injury markers before and after treatment were compared between the two groups. Results After treatment, the total effective rate of clinical treatment in the observation group was higher than that in the control group; the recovery time of CHE activity, coma time , hospitalization time in the observation group were shorter than those in the control group, and the dosage of Atropine was less than that in the control group; after treatment, CHE levels in both groups increased, and the observation group was higher than the control group; the levels of serum NSE, CK, LDH, CK-MB and IMA in both groups decreased, and those in the observation group were lower than those in the control group (all P<0.05). Conclusion? Sequential blood purification can quickly restore the serum CHE activity of patients with acute severe organophosphorus poisoning by improving the toxin clearance rate, thereby reducing the use of Atropine, reducing the damage of the patient's myocardial and nervous system, and further shortening the coma and hospitalization time, and improving the treatment effect.