Abstract: Objective To explore the efficacy of extremely low-dose rituximab for primary refractory nephrotic syndrome and examine its influence on renal function，immunoglobulins and Toll-like receptors（TLRs）. Methods From March 2017 to February 2020，72 patients with primary refractory nephrotic syndrome were selected as research subjects and randomized into 3 groups（n=24 each）. Group A received extremely low-dose rituximab（100 mg），group B standard dose rituximab（375 mg/m²）and group C hormone therapy. Clinical efficacy，incidence of adverse reactions and renal function parameters ［serum creatinine（Scr），blood urea nitrogen（BUN），24-hour urine protein quantitative］，immunoglobulins［immunoglobulin（Ig）A，IgG，IgM］，serum inflammatory factors［tumor necrosis factor-α （TNF-α），interleukin-6（IL-6）］and TLRs（TLR4，TLR7）levels were statistically compared among three groups. Treatment expenses of rituximab were compared between groups A and B. Results The clinical remission rate of group A/B was higher than that of group C（P<0.05）. After 2/4-week treatment，the quantitative levels of Scr，BUN and 24 h-urinary protein were lower in group A/B than those in group C. And IgA， IgG and IgM were higher than those in group C（P<0.05）. After 2/4-week treatment，serum levels of TNF-α，IL-6，TLR4 and TLR7 were lower in group A/B than those in group C （P<0.05）. No significant difference existed in serum levels of TNF-α， IL-6， TLR4 and TLR7 between groups A and B（P>0.05）. The incidence of adverse reactions was lower in group A than that in group B/C（P<0.05）and no significant difference existed in the incidence of adverse reactions between groups B and C（P>0.05）. Treatment expense of rituximab was lower in group A than that in group B（P< 0.05）. Conclusion For primary refractory nephrotic syndrome，extremely low-dose rituximab can significantly improve renal and immune functions，lower the level of Toll-like receptors，reduce the incidence of adverse reactions and curtail treatment expenses. It is worthy of wider clinical applications.