Objective To analyze the significance of the combined detection of anti-double-stranded DNA （anti-dsDNA） antibody quantification， antinuclear antibody （ANA）， and anti-neutrophil cytoplasmic antibody （ANCA） in the diagnosis and assessment of the severity of systemic lupus erythematosus （SLE）. Methods A total of 154 SLE patients （SLE group， comprising 115 active cases and 39 inactive cases） who were admitted to the Department of Rheumatology and Immunology， the First Affiliated Hospital of Anhui Medical University between May and December 2024， 100 non-SLE patients （non-SLE group）， and 50 healthy volunteers （control group） were simultaneously enrolled in this study. Clinical data as well as the test results of anti-dsDNA， ANA， and ANCA were compared across the groups. The correlation between the positivity of anti-dsDNA， ANA， and ANCA and renal damage， along with the SLE disease activity index （SLEDAI） score in active SLE patients， was analyzed. Binary logistic regression was employed to identify the risk factors for active SLE， and receiver operating characteristic （ROC） curves were plotted to assess the value of anti-dsDNA， ANA， and ANCA in evaluating active SLE. Results The positive rates of anti-dsDNA， ANA， and ANCA in the SLE group were 55.84% （86 out of 154）， 100% （154 out of 154）， and 22.08% （34 out of 154）， respectively. Among the individuals testing positive for ANA， the predominant fluorescent patterns in SLE cases were the homogeneous pattern （42.85%， 66 out of 154）， the nuclear granular pattern （23.38%， 36 out of 154）， and the related mixed pattern （29.22%， 45 out of 154）. The positive rates of anti-dsDNA and ANCA in the SLE group were significantly higher than those in the non-SLE group （P < 0.05）. The incidence of renal damage， SLEDAI scores， IgA， IgM， and IgG levels， as well as the positive rates of anti-dsDNA and ANCA， were notably higher in patients with active SLE compared to those with inactive SLE， whereas the serum complement C3 and C4 levels were lower in active patients （P < 0.05）. In patients with active SLE， the positive rates of anti-dsDNA， ANA， and ANCA were positively and significantly correlated with renal damage and SLEDAI score （P < 0.05）. SLEDAI score， anti-dsDNA positivity， and ANCA positivity were identified as independent risk factors for active SLE （P < 0.05）. The area under the curve （AUC） of the combination of SLEDAI score， anti-dsDNA， and ANCA for predicting active SLE was 0.819 （95%CI： 0.738 ~ 0.900）， which was significantly greater than that of each indicator alone （Z = 2.291， 2.638， 4.848， P < 0.05）. Conclusion Anti-dsDNA， ANA， and ANCA are highly valuable for detection in patients with SLE. Specifically， anti-dsDNA and ANCA are closely associated with disease activity and renal damage. Conducting tests on these markers can effectively assist in the evaluation of the patients'condition.