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In order to investigate and analyze the caries status of permanent first molars (PFMs) in children aged 10 to 12 years in Southern China and to analyze the related factors, from January to August 2019, a multi-stage, stratified, cluster, and random sampling method had been used to select 6208 children from 22 schools in Guangzhou city for oral health examinations and questionnaires. The total caries rate of the PFMs was 39.40%, total DMFT score was [Formula: see text], the filling rate of caries was 3.38%, and the rate of fissure sealant was 5.89%. The percentage of PFM caries was statistically significant between female and boys, urban and rural areas, only-children and non-only children, and between ethnic minorities and Han ethnic groups ([Formula: see text]). The difference between urban and rural areas was statistically significant ([Formula: see text]). Multivariate logistic regression analysis showed that the number of daily toothbrushes, the number of desserts eaten, milk drinking before bedtime, being the only-child, and the parents’ level of education were the independents influencing the factors of for developing dental caries. The incidence of dental caries in the PFMs of children aged 10–12 years in Southern China is high, and the rate of fissure sealant and the rate of dental fillings are low. There are a lot of differences between urban and rural areas, where children’s oral health knowledge is poor, and poor oral hygiene behaviors and dietary habits exist.