Objective To analyze the correlation between serum C-reactive protein (CRP), cystatin C (Cys-C), and beta-2-microglobulin (β2-MG) levels and the disease activity and renal function of systemic lupus erythematosus (SLE), and to explore their evaluation value for renal function injury. Methods A total of 102 SLE patients admitted to our hospital from March 2021 to March 2023 were included in the study group, and 34 healthy volunteers who underwent physical examination at our hospital during the same period were included in the control group. The patients were divided into 22 cases of no activity, 26 cases of mild activity, 34 cases of moderate activity and 20 cases of severe activity according to the SLE disease activity index (SLEDAI). The serum CRP, Cys-C, and β2-MG levels were compared, and the correlation with disease activity was analyzed. According to the estimated glomerular filtration rate (eGFR), the patients were divided into 43 patients with normal renal function and 59 patients with renal function impairment, and the changes in serum CRP, Cys-C, and β2-MG levels were compared. The receiver operating characteristic curve (ROC) was adopted to evaluate its value in evaluating renal function impairment. Results The levels of serum CRP, Cys-C, and β2-MG in the study group were higher than those in the control group (P<0.05). As the disease activity increases, the levels of serum CRP, Cys-C, and β2-MG show a rising trend (P<0.05). Serum CRP, Cys-C, and β2-MG were positively correlated with disease activity （r _CRP=0.536,P=0.009;r _Cys-C=0.574,P=0.006;r _β2-MG=0.602,P=0.001）. The levels of serum CRP, Cys-C, and β2-MG in patients with renal function impairment were higher than those in patients with normal renal function (P<0.05). The area under the curve AUC of serum CRP, Cys-C, β2-MG, and their combined detection for evaluating renal function injury were 0.711, 0.755, 0.792, and 0.929, respectively, and the AUC of combined evaluation was greater than that of individual indicators (P<0.05). Conclusion The levels of serum CRP, Cys-C, and β2-MG in SLE patients are elevated and positively correlated with disease activity. Combined detection of their levels has certain evaluation value for renal function injury.