Objective To analyze the effects of different frequency of hemodiafiltration combined with high flux hemodialysis (HFHD) on the clearance of uremic toxins and prognosis of uremia.Methods A total of 122 patients with uremia who received hemodialysis in our hospital from July 2016 to July 2021 were selected and divided into the control group and the research group randomly, with 61 cases in each group. Both groups were given hemodiafiltration and HFHD treatment. The frequency of HFHD treatment was consistent between the two groups. In contrast, the control group was treated with hemodiafiltration once a month, while the study group was treated with hemodiafiltration once a week. The two groups were followed up for 12 months from the start of treatment. The clearance of uremic toxins, nutritional status, levels of inflammatory factors and renal function of the two groups before and after the treatment were compared. The drug use and short-term prognosis of the two groups were also compared.Results The differences of serum levels of calcium, phosphorus and potassium before and after the treatment in the study group were higher than those in the control group (P < 0.05). The differences of the levels of hemoglobin, serum albumin and transferrin before and after the treatment in the study group were higher than those in the control group (P < 0.05). The differences of the levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) before and after the treatment in the study group were higher than those in the control group (P < 0.05). The differences of the levels of blood urea nitrogen and serum creatinine and residual urine volume before and after the treatment in the study group were higher than those in the control group (P < 0.05). The differences of the dosages of erythropoietin and intravenous iron before and after the treatment in the study group were higher than those in the control group (P < 0.05). There was no significant difference in the overall incidence of adverse events between the two groups (P > 0.05).Conclusions Compared with hemodiafiltration once a month, that once a week clears the uremic toxins more effectively, improves the nutritional status and renal function of uremia patients, and reduces the levels of inflammatory factors and dosages of erythropoietin and intravenous iron when combined with HFHD.