Objective To explore the clinical characteristics and related factors of SARS-CoV-2 Omicron variant infection in children. Methods The clinical manifestations, laboratory tests, pulmonary CT imaging, nucleic acid detection, clinical typing, vaccination and therapeutic efficacy of 94 children with Omicron infection were analyzed and summarized. Results A total of 94 children were enrolled, including 51 boys (54.3%) and 43 girls, aged from 9 days to 14 years (mean, 4.5±3.3 years), 33 of whom had been vaccinated. All children had a history of close contact with Omicron infected patients. Asymptomatic and mild cases accounted for 76.6%. The mean value of peripheral blood absolute lymphocyte count in pneumonia group was 2.66×10⁹/L, which was significantly lower than that (4.18×10⁹/L) in asymptomatic/mild group (P=0.024). Compared with non-vaccinated group, the proportion of asymptomatic and mild cases was significantly higher (90.9% vs 68.9%, P=0.013), the number of children with fever was lower (42.4% vs 70.5%, P=0.008), and the average length of hospital stay was significantly shorter (P=0.026) in vaccinated group. The C_t values of ORF1ab and N gene in vaccinated group were significantly higher than those in non-vaccinated group (P<0.05). Individualized syndrome differentiation and treatment was carried out by adding or subtracting classic prescription of traditional Chinese medicine decoction and empiric antibiotics (cephalosporins or macrolides) were administered in combination. All patients recovered, and the average hospital stay was (8.5±3.8) days. One severe case was controlled in time by comprehensive therapy including active anti-secondary infection, anticoagulant drugs and short course glucocorticoids. Conclusions Children are generally susceptible to the Omicron strains, and vaccination helps to improve specific immunity. Therefore, strengthening isolation and vaccination are effective measures to prevent Omicron infection in children.