Objective To explore the effect of rituximab on cellular immunity and cytokines in children with new-onset steroid-sensitive nephrotic syndrome (SSNS). Methods Clinical data of 60 children with new-onset SSNS treated at Xuzhou Children's Hospital from December 2021 to March 2023 were retrospectively analyzed. Children were allocated according to rituximab use into a control group (no rituximab) and an observation group (rituximab). The relapse rate, T-lymphocyte subsets and cytokines before and after treatment, and the incidence of adverse reactions were compared between groups. Results The relapse rate was lower in the observation group than in the control group (27% vs 73%, P<0.05). After treatment, CD3⁺ and CD4⁺ T-lymphocyte counts, the CD4⁺/CD8⁺ ratio, and serum interleukin-2 increased in the observation group and were higher than in the control group (P<0.05). Interleukin-6 and tumor necrosis factor-α levels decreased after treatment in the observation group and were lower than in the control group (P<0.05). After treatment, CD8⁺ T-lymphocyte counts decreased, interferon-γ increased, and interleukin-10 decreased in both groups, with no significant differences between the two groups (P>0.05). The incidence of adverse reactions did not differ significantly between the two groups (P>0.05). Conclusions Rituximab can reduce the relapse rate in children with new-onset nephrotic syndrome and shows good safety. Its therapeutic effect is achieved by regulating the number and function of T cells and by modulating the anti-inflammatory effects of cytokines.