Anti-complement factor H (CFH) autoantibody-associated hemolytic uremic syndrome (HUS) is a severe sub-type of HUS. We assessed the clinical and renal pathological features, circulating complement levels, and genetic background of Chinese pediatric patients with this sub-type of HUS. Thirty-three consecutive patients with acute kidney injury who tested positive for serum anti-CFH autoantibodies were enrolled in this study. All of the eight patients who underwent renal biopsies presented with changes typical of thrombotic microangiopathy, especially changes in chronic characteristics. Compared to patients in remission and normal control subjects, patients with acute disease had significantly lower plasma CFH levels and significantly higher plasma complement 3a (C3a), C5a, and terminal complement complex (SC5b-9) levels. The CFH-anti-CFH immunoglobin G (IgG) circulating immunocomplex (CFH-CIC) titers were more closely correlated with CFH plasma levels than anti-CFH IgG levels. Of the 22 patients, four (18%) were homozygous for CFHR3-1 Delta and ten were heterozygous for CFHR1 or CFHR3 deletions. Most patients responded well to a combination of plasma and immunosuppressive therapies, with a remission rate of 87%. At the end of the follow-up, nine patients reached the combined end-points, including two with end-stage renal disease and seven with relapses. Plasma C3a, C5a, and SC5b-9 levels predicted disease activity in anti-CFH autoantibody-associated HUS patients enrolled in this study. These patients responded well to plasma therapy combined with immunosuppression.