Objective: To assess the diagnostic efficacy of serum free light chain (sFLC) levels in differential diagnosis of monoclonal gammopathies of renal significance, and to evaluate the correlation between sFLC and stages of kidney disease caused by various etiologies. Methods: Three hundred and sixty-eight patients with non-monoclonal gammopathy-related nephropathy, 64 patients with monoclonal gammopathy of renal significance, and 30 normal individuals were enrolled from Shanghai Ruijin Hospital from January 2017 to September 2021. The sFLC levels were measured by IMMAGE 800 Protein Chemistry Analyzer (Beckman, USA). The statistical analysis was carried out by GraphPad Prism v9.0. Results: The sFLC levels in patients with monoclonal gammopathy were significantly higher than that in patients with non-monoclonal gammopathy (sFLCκ：453.0 mg/L vs. 53.2 mg/L; sFLCλ：382.5mg/L vs. 56.5mg/L, respectively), and the sFLCκ/λ ratio was abnormal. The best predictive value for diagnosing monoclonal gammopathy with kappa light-chain isotype was achieved using a cut-off value of sFLCκ/λ ratio at 1.952 (AUC 0.933 9; sensitivity 84.4%; specificity 97.0%). The best predictive value for diagnosing monoclonal gammopathy with lambda light-chain isotype was achieved using a cut-off value of sFLCκ/λ ratio at 0.455 (AUC 0.915 9; sensitivity 84.4%; specificity 87.2%). The correlation between sFLC levels and stages of kidney disease （r=0.7） was stronger in patients with non-monoclonal gammopathy compared with those with monoclonal gammopathy （r=0.4）. The correlation coefficients between sFLC levels and kidney disease stages are higher than those of the sFLCκ/λ ratio （r<0.3）. Conclusions: The sFLCκ/λ ratio could be used for differential diagnosis of monoclonal gammopathy of renal significance, whereas sFLC levels are more suitable for the evaluation of renal function in patients compared with sFLCκ/λ ratio.