The aim of the present study was to investigate the impact of three different blood purification methods, hemoperfusion (HP), continuous blood purification (CBP), and on-line high-volume hemodiafiltration (OL-HDF), on the survival rate of patients with acute severe organophosphorus pesticide poisoning (ASOPP), as well as on major pro-inflammatory (interleukin [IL]-1, IL-6, tumor necrosis factor-α [TNF-α]) and anti-inflammatory (IL-10) cytokines in the serum. Eighty-one ASOPP patients were randomly divided into three groups: HP (N = 23), HP + CBP (N = 26), HP + OL-HD (N = 32). Serum IL-1, IL-6, TNF-α, and IL-10 levels were assessed by ELISA before treatment and at 24 and 48 h post-treatment and survival rates were determined. Patient survival rate was significantly higher in OL-HDF and CBP treated patients compared with HP group (P < 0.05). A significantly greater clearance effect in serum IL-1, IL-6, and TNF-α levels at 24 and 48 h post-treatment was observed in CBP and OL-HDF groups compared with the HP group (P < 0.05). The levels of serum anti-inflammatory cytokine IL-10 increased significantly in CBP and OL-HDF groups compared with the HP group (P < 0.05 at 48 h post-treatment). In addition, OL-HDF treatment achieved similar changes in serum TNF-α, IL-1, IL-6 and IL-10 levels as CBP (P > 0.05). Compared with the HP method, CBP or OL-HDF combined with HP can rapidly clear inflammatory cytokines, reduce systemic inflammatory response syndrome, and improve the survival of ASOPP patients. Compared with CBP, OL-HDF is an economical and effective method to treat ASOPP with less technical difficulty and more suitability for rural areas and primary hospitals.