SARS-CoV-2 has ravaged the world and undergone multiple mutations during the course of the COVID-19 pandemic. On 7 April 2022, an epidemic caused by SARS-CoV-2 Omicron (BA.2) variant broke out in Guangzhou, China, one of the largest transportation and logistical hubs of the country.To fast curtained the Omicron epidemic, based on the routine surveillance on the risk population of SARS-CoV-2 infection, we identify key places of the epidemic and implement enhanced control measures against Omicron.Transmission characteristics of the Omicron variant were analyzed for 273 confirmed cases, and key places involved in this epidemic were fully presented. The median incubation time and the generation time were 3 days, and the reproduction number Rt was sharply increased with a peak of 4.20 within 2 days. We tried an all-out effort to tackle the epidemic in key places, and the proportion of confirmed cases increased from 61.17% at Stage 2 to 88.89% at Stage 4. Through delimited risk area management, 99 cases were found, and the cases were isolated in advance for 2.61 ± 2.76 days in a lockdown zone, 0.44 ± 1.08 days in a controlled zone, and 0.27 ± 0.62 days in a precautionary zone. People assigned with yellow code accounted for 30.32% (84/277) of confirmed COVID-19 cases, and 83.33% of them were detected positive over 3 days since code assignment. For the districts outside the epicenter, the implementation duration of NPIs was much shorter compared with the Delta epidemic last year.By blocking out transmission risks and adjusting measures to local epidemic conditions through the all-out effort to tackle the epidemic in key places, by delimiting risk area management, and by conducting health code management of the at-risk population, the Omicron epidemic could be contained quickly.Copyright © 2022 Cai, Yang, Liang, Lin, Ma, Chen, Li, Li, Mai, Mai, Kong, Liang, Li, Tu, Chen, Hon, Qin, Li, Li, Miao, Liu, Guan, Zeng, Qiu, He, Zhang, Yang and Zhong.