Childhood-onset systemic lupus erythematosus (SLE) can be more severe than adult patients. Early diagnosis and accurate evaluation of the disease are very important for the patients. Response gene to complement-32 (RGC-32) protein is the downstream regulator of C5b-9 complex which is the terminal pathway of complement activation. Complement system plays a very important role in the pathogenesis of SLE. RGC-32 in patients with SLE has not been reported yet. We aimed to examine the clinical value of RGC-32 in children with SLE. A total of 40 children with SLE and another 40 healthy children were enrolled for this study. Clinical data were obtained prospectively. Serum RGC-32 was determined by ELISA. We found that serum RGC-32 was significantly elevated in children with SLE than that in the healthy group. Serum RGC-32 was significantly higher in the children with moderately/severely active SLE than that in the children with no/mildly active SLE. Furthermore, serum RGC-32 level correlated positively with C-reactive protein, erythrocyte sedimentation rate and ferritin and correlated negatively with white blood cell counts and C3. RGC-32 may be involved in the pathogenesis of SLE. RGC-32 might become a good biomarker in the diagnosis and evaluation of SLE.