Childhood asthma and obesity have posed a parallel epidemic over the past few decades. However, whether asthma diagnosis is associated with obesity, and what the roles of lifestyle factors play in this relationship, remained unclarified. This study aimed to investigate the association between asthma and weight status in Chinese children and explore the potential mediating and/or modifying roles of lifestyle factors in the association. In this cross-sectional study, 16,837 children aged 6-12 years were recruited from Guangzhou, China. Participants’ information on physician-diagnosed asthma was collected from parents, and data on physical activity, screen time, and sleeping were reported in a validated questionnaire. Height and weight were objectively measured, and weight status was classified by body mass index (BMI). Multiple logistic regression analysis and mediation analysis were used. Results showed that asthmatic children were at significantly higher risk of obesity (odds ratio () 1.51, 95% confidence interval () 1.03, 2.21) compared with non-asthmatic children. More importantly, this increased risk was even greater in children with moderate-to-vigorous physical activity <60 min/d and children with screen time >2 h/d (both < 0.05). Also, a positive relationship of asthma with overweight was found in children with screen time >2 h/d ( 3.92, 95% 1.56, 9.88), while a negative association was observed between asthma and underweight in children aged 9-12 years ( 0.23, 95% 0.06, 0.92). Mediation analysis indicated that these associations were not mediated by physical activity, screen time, or sleeping. The findings suggested that physician-diagnosed asthma was associated with higher risks of overweight and obesity, and these risks might be exacerbated by insufficient physical activity and prolonged screen time.