Abstract: ABSTRACT Objective: To investigate the effects of hemoperfusion combined with hemodialysis (HP+HD) and hemodiafiltration (HDF) on different molecular weight substances in maintenance hemodialysis (MHD) patients. Methods: Sixty patients undergoing maintenance hemodialysis (HD) for more than 3 months in our hospital were randomly divided into the Group A (HDF, n=30) and Group B (HP+HD, n=30). Patients in Group A received HDF, whereas patients in Group B received combined HP+HD once a week. Each patient received HD twice a week moreover. The levels of blood urea nitrogen (BUN), Single urea clearance index (KT/V) calculated by the formula Daugirdas, and serum albumin (Alb), beta 2-microglobulin (β2-MG), intact parathyroid hormone (iPTH), C-reactive protein (CRP) based on clinical routine testing, and Leptin, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) detected by protein chip suspension, were compared between the two groups. The adverse reactions associated with the therapy, important complications and mortality were observed. Results: There were no significant differences of Kt/V, the clearance rates of iPTH and β2-MG between the two groups. The reduction rates of macro-molecules, such as Leptin, IL-6, and TNF alpha in Group B were higher than those in group A. After six month, levels of inflammatory markers, such as IL-6, TNF alpha and CRP, in group B were significantly lower, and nutritional status and quality of life is better than those in group A. Conclusion: There was no significant differences in clearance rate of serum small and medium molecular substances between HP+HD and HDF. HP+HD can effectively reduce the level of macro-molecules, such as Leptin, IL-6, TNF alpha and CRP, alleviate inflammatory status, improve nutritional status and quality of life.