Detection of autoantibodies in systemic lupus erythematosus (SLE) plays an important role in timely diagnosis and earlier treatment of SLE. In this study, we used a SmD1 polypeptide-based ELISA to determine anti-SmD1 antibody in 269 SLE, including100 naïve (had not been treated with steroids or immunosuppressants at study inception) SLE patients and 169 non-naive SLE patients; 233 controls with other rheumatic diseases (RDC) (70 RA, 40 AS, 73SSc, and 50 SS), and 110 healthy controls (HC) group. The positive rate of anti-SmD1 among all SLE patients was 60.97%, higher than that in the RDC group (13.30%, P = 0.000) or the HC group (9.09%, P = 0.000). The positive rate of anti-SmD1 in non-naive SLE patients was higher than that for anti-dsDNA antibodies (44.97%, P = 0.03). Positivity for anti-SmD1 only was found in 14.00% of naive SLE patients and 16.00% of non-naive SLE patients. In naive SLE patients, the serum concentration of anti-SmD1 was lower after treatment than before treatment (P = 0.039). Active SLE patients positive for anti-SmD1 were more likely to have malar rash, rash, nonscarring alopecia, PAH and hypocomplementemia. High positivity for anti-SmD1 only in patients with SLE indicated the importance and necessity of detection of anti-SmD1 in patients with SLE.