Objective To analyze the epidemic characteristics of varicella and the genetic characteristics of varicella zoster virus (VZV) in Yangzhou in 2021, and to provide a theoretical basis for the scientific prevention and control of varicella in Yangzhou. Methods Descriptive epidemiological analysis was carried out on the varicella outbreaks reported in Yangzhou in 2021. Throat swabs or herpes fluid samples from varicella cases in 2021 were collected, and the viral nucleic acid was detected by real-time fluorescent quantitative PCR. The genotype and evolutionary relationship of the virus strain were determined according to the 6 SNPs in the ORF22 gene fragment sequence. Results In 2021, there were 20 varicella outbreaks in Yangzhou, involving 147 cases, all of which occurred in kindergartens and primary and secondary schools, and the peak incidence was in the age group of 4-7 years old. The high incidence time of the outbreaks was from May to July, and from November to January of the next year. The varicella vaccination rate of the cases was low, and all were 1-dose vaccination. The gene sequencing results of 8 samples were J/clade 2, and 3 of them had A-C synonymous mutation at position 37997 in ORF22 sequence. Conclusion In 2021, varicella outbreaks in Yangzhou occurred mainly in kindergartens and schools. Preschool children are susceptible, all of which are caused by J/clade 2 varicella-zoster virus. It is suggested to strengthen the monitoring and management of the varicella epidemic situation in schools in the city, and at the same time incorporate the varicella vaccine into the routine immunization program of the city and strengthen 2 doses of varicella vaccination.