Objective To investigate the effect of timing of hemoperfusion (HP) on the efficiency of hemodialysis (HD) combined with HP, a kind of combined artificial kidney (CAK), in treating patients on maintenance hemodialysis. Methods Totally 20 end-stage renal disease patients undergoing hemodialysis (HD) (4 hours every time,3 times every week)for more than 3 months in the Blood Purification Department of Shanghai Tongji Hospital were enrolled in the present study from July 2012 to January 2013. All patients were alternately and randomly given two kinds of CAK (model A: HP was given during the first and second hours of HD; model B: HP was given during the third and forth hours of HD) in succession. Serum samples were harvested before and after CAK treatment and the toxin concentrations were measured in the same batch; the toxin concentrations after CAK were corrected by pre-treatment body weight and ultrafiltration quality. Efficiencies of different models of CAK were evaluated by the absolute and percentages of toxin concentration declines after treatment. Results All the toxins were significantly declined after treatment with both models of CAK (P<0.01). The clearance efficiencies for serum creatine (SCr) and blood urea nitrogen (BUN) were not significantly different between the two models (P＞0.05). The decreases of intact parathyroid hormone (iPTH) and β₂-microglobulin (β₂-MG) of model B were significantly greater than those of model A (P<0.05). Model B also led to significantly greater decline of interleukin-1(IL-1), interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α), either in absolute value and/or percentage (P<0.05). The declines of C-reactive protein (CRP) and pentraxin 3(PTX-3) and the incidences of adverse events (low blood pressure, blood coagulation and so on) were not significantly different between the two models(P＞0.05). Conclusion Both models of CAK are significantly efficient in eliminating uremic toxins for MHD patient. Comparatively, model B CAK have better performance for eliminating iPTH, β₂-MG, IL-1, IL-6 and TNF-α, without increasing adverse events, and is worth of popularizing in clinic.