Objective To analyze the value of Antinuclear antibody (ANA) and anti-double-stranded DNA antibody (distrand-DNA) for the diagnosis of Systemic lupus erythematosus (SLE). Methods 104 patients diagnosed with SLE admitted to our hospital from March 2022 to April 2024 were included in the SLE group. Another 83 patients with other autoimmune diseases admitted in the same period were included in the non-SLE group. Detection of anti-nuclear antibody and anti-double-stranded DNA antibody. The positive rates of ANA and dsDNA antibodies in SLE group and non-SLE group were analyzed and compared. The positive rates of ANA and dsDNA antibodies in active and inactive SLE patients were compared. The diagnostic efficacy of ANA and dsDNA antibody alone and in combination with SLE were compared, and their consistency with immunological examination results were compared. Results The positive rates of ANA and dsDNA antibody in SLE group were significantly higher than those in non-SLE group (P<0.05). There was no significant difference in the positive rates of ANA and dsDNA antibody between active and non-active SLE patients (P>0.05). The sensitivity, specificity, accuracy, positive predictive value and negative predictive value of ANA combined with dsDNA antibody for SLE were 97.11%, 98.79%, 97.86, 99.02% and 96.47%, respectively, which were higher than ANA and dsDNA antibody alone. The sensitivity of ANA+dsDNA antibody and ANA test was higher than that of dsDNA antibody test, the specificity and positive predictive value of ANA+dsDNA antibody and dsDNA antibody test were higher than that of ANA test, and the accuracy and negative predictive value of ANA+dsDNA antibody test were higher than that of ANA test and dsDNA antibody test (P<0.05). The consistency Kappa values of ANA, dsDNA antibody alone and combined diagnosis of SLE and immunological examination were 0.764, 0.773 and 0.975 respectively, with the highest consistency of combined diagnosis. Conclusion ANA combined with dsDNA antibody can make up for the shortcomings of the two methods alone, improve the diagnostic efficiency of SLE and reduce the risk of missed diagnosis.