Background <p>Although previous studies have explored many risk factors associated with childhood asthma worldwide, limited studies have examined whether these risk factors differ in different regions. Our study aims to investigate whether there are differences in the factors influencing childhood asthma in Northern and Southern China and to explore possible reasons for this.</p> Methods <p>A cross-sectional analysis of 12,771 urban children aged 4-14 in China, we first applied a group Least Absolute Shrinkage and Selection Operator (LASSO) to influencing factors associated with childhood asthma, using cross-validation as the criterion. Then, we used logistic regression to calculate further the results. The Area Under the curve value used to evaluate model performance.</p> Results <p>In Northern China, risk factors for childhood asthma include boys, previously hospitalized with eczema/dermatitis or asthmatic bronchitis or chronic cough, history of infected with viral, bacterial or mycoplasma, testing positive for allergens, having conjunctivitis or two or more allergy problems, paternal or maternal with asthma or conjunctivitis or eczema/dermatitis, autumn and winter and house decoration less than 1 year before move in; Older than 11 years and the frequency of airing the quilt are protective factor against asthma. In Southern China, risk factors include antibiotic use in neonates, previously hospitalized with asthmatic bronchitis, history of infected with viral, testing positive for allergens, having conjunctivitis, summer or winter, screen time more than 4&#xa0;h per day and paternal or maternal with rhinitis.</p> Conclusions <p>Our findings suggested that risk or protective factors contributing to childhood asthma differ significantly between Northern and Southern China.</p>