Abstract: Objective To evaluate the clinical significance of plasmablasts and B-cell activating factor (BAFF) expression in the peripheral blood of children with steroid-sensitive nephrotic syndrome (SSNS). Methods A total of 54 SSNS children who were admitted to Department of Pediatrics, the Affiliated Hospital of Xuzhou Medical University from June 2022 to June 2024 were selected, and their clinical data were collected for retrospective analysis. According to disease recurrence and treatment strategies, the children were divided into a relapse group (n=26) and a remission group (n=28). Their peripheral venous blood samples were collected to detect the urine protein/creatinine ratio (ACR) and the percentage of peripheral blood B lymphocyte subsets. The absolute number of B lymphocyte subsets were calculated. The concentrations of serum BAFF and interleukin-21 (IL-21) were measured by ELISA. The levels of IgG and IgM in the samples were examined by immunoturbidimetry. The correlation between the absolute number of plasmablasts in the relapse phase and the detected indicators was analyzed. Results Compared with the children in the remission phase, those in the relapse phase showed significant increases in ACR and serum IgM levels, decreases in IgG levels, and increases in serum BAFF and IL-21 concentrations (P<0.05). The percentage of plasmablasts was significantly higher in the relapse phase than that in the remission phase (P<0.05), while there was no statistical difference in the percentages of other B-cell subsets (P>0.05). The absolute number of plasmablasts in the relapse phase was positively correlated with ACR, BAFF, and IL-21 concentrations, and IgM levels, while negatively correlated with IgG levels (P<0.05). Conclusions The absolute number of plasmablasts in the peripheral blood of SSNS children is associated with the severity of the disease. The increase in plasmablasts and serum BAFF concentrations may have potential predictive value for SSNS relapse.