Objective To evaluate the diagnostic value of anti-SmD1 antibody in systemic lupus erythematosus(SLE). Methods In serum samples from 60 cases with SLE, 54 cases with other autoimmune disease, and 50 healthy persons(control group), following were studied: levels of anti-SmD1 antibody by ELISA, anti-double strain DNA(dsDNA)antibody by indirect immunofluorescent assay, as well as anti-Sm antibody by immunoblotting assay, anti-nucleosome antibody(AnuA)by immunoblotting assay, and anti-ribosomal P protein antibody(ARPA)by immunoblotting assay. Results The level and positive rate of serum anti-SmD1 antibody in SLE group were 31.55(13.98～128.84)U/mL and 53.3%(32/60), which were significantly higher than that in other autoimmune disease group 13.48(12.50～19.80)U/mL, 14.8%(8/54)and control group 13.62(12.50～17.93)U/mL, 2.0%(1/50)(P<0.01). Among 5 SLE serological markers, anti-SmD1 antibody showed the highest diagnostic sensitivity of 53.3%(32/60), negative predictive value of 77.2%(95/123)and accuracy of 77.4%(127/164). Meanwhile, there were no significant consistencies on distribution of anti-SmD1 antibody with AnuA and ARPA in SLE group(P>0.05). The combined detection of anti-SmD1 antibody with conventional serological markers including anti-dsDNA antibody, anti-Sm antibody, AnuA and ARPA increased the sensitivity to 71.7%(33.3%), which was significantly higher than detection of anti-SmD1 antibody alone. Furthermore, the area under receiver operating characteristic curve ROC of the combined detection of anti-SmD1 antibody with conventional serological markers was 0.827, which was higher than detection of anti-SmD1 antibody(0.733)alone or the detection of conventional serological markers combined(0.765). Conclusions Anti-SmD1 antibody has favorable diagnostic value over the conventional serological markers, and it has complementary effect when used with the conventional serological markers in SLE. The combined detection of anti-SmD1 antibody with conventional serological markers contributes to increased diagnostic sensitivity of SLE.