Objective: This study aimed to compare the efficacy and safety of low-dose rituximab (RTX, 100 mg/month) versus belimumab (BEL, 10 mg/kg), as a control, in the treatment of systemic lupus erythematosus (SLE). Methods: A retrospective analysis was conducted on 117 SLE patients who received low-dose RTX (n=51) or BEL (n=66) at Fujian Medical University Union Hospital between January 2020 and June 2023. Data on baseline characteristics, laboratory parameters (platelet count, creatinine, proteinuria, complement C3/C4, erythrocyte sedimentation rate (ESR)), disease activity (SLEDAI-2K), glucocorticoid dosage, concomitant immunosuppressant use, efficacy assessments, and adverse events were collected. Paired t-tests or Wilcoxon tests were used for within-group comparisons, and independent-sample t-tests or Mann-Whitney U tests for between-group comparisons. Results: > 0.05), with no unexpected safety signals. Concomitant immunosuppressant use also varied between groups, with mycophenolate mofetil (MMF) more common in BEL and Cyclosporine A (CsA) in RTX. Conclusion: Low-dose RTX (100 mg/month) can be regarded as a treatment option for SLE, based on its comparable efficacy to BEL in improving disease activity, increasing platelet count, and ameliorating proteinuria. Although BEL shows greater advantages in reducing glucocorticoid dosage and improving hypercoagulability, the overall evidence supports low-dose RTX as an effective and safe alternative for SLE, with a favourable safety profile.