<b><i>Background:</i></b> Atypical hemolytic uremic syndrome (aHUS) is a rare but critical illness. To this date, few studies have reported on the disease in Chinese children. <b><i>Methods:</i></b> We studied a Chinese pediatric cohort to delineate the clinical characteristics, genotypes, and prognosis. Ninety-one patients with aHUS were enrolled in this study. <b><i>Results:</i></b> Fifty-nine children (64.8%) had anti-complement-factor-H autoantibody-associated aHUS (anti-CFH aHUS). Of these children, 21 (46.7%) had complement factor-H-related protein 1 (CFHR1) homozygous deletion, and most patients with CFHR1 homozygous deletion also had complement factor-H-related protein 3 (CFHR3) homozygous deletions (76.2%). Using gene sequencing of 15 candidate genes, we identified 14 genetic variants in 46 aHUS patients, including 5 pathogenic or like pathogenic variants and 9 variants of uncertain significance. The average follow-up time was 46.1 ± 28 months. Among patients with anti-CFH aHUS, there was a correlation between CFHR1 homozygous deletion and patients with persistent proteinuria (odds ratio [OR] 6.954, 95% confidence interval [CI] 1.033–46.821, <i>p</i> = 0.046). As of the last follow-up, ESRD or deaths occurred in 3.6% of the children with anti-CFH aHUS and 26.7% of children with aHUS who were negative for anti-CFH. <b><i>Conclusions:</i></b> Anti-complement-factor-H antibody positivity is the main cause of morbidity in Chinese children with aHUS. There may be a correlation between CFHR1 homozygous deletion and persistent proteinuria. Comprehensive assessment of anti-CFH antibodies and genetic variants is essential for the management of aHUS children.