OBJECTIVE To investigate associations of five typical lifestyle-related behavioral risk factors (insufficient physical activity, prolonged screen viewing, deprived sleeping, consumption of fast food and sugar-sweetened beverage) with health-related quality of life (HRQoL) among school students in China. METHODS Students aged 9-17 years (grades 4-12) were randomly selected from primary and high schools in Nanjing, China, to participate in this cross-sectional study in 2018. The outcome variable, HRQoL, was assessed using the Child Health Utility 9D (CHU9D) instrument and scored from 0 (worst) to 1 (best). Physical activity (including screen viewing and sleeping) and dietary intake were measured using a validated Physical Activity Scale and Food Frequency Questionnaire, respectively. Lifestyle-related behaviors were categorized as sufficient/insufficient or no/yes, and their associations with HRQoL were assessed using mixed-effects linear regression models. RESULTS Overall, 4388 participants completed the questionnaire (response rate = 97.6%). Students with insufficient physical activity [mean difference (MD) = - 0.03; 95% confidence interval (CI) = - 0.04, - 0.01], prolonged screen time (MD = - 0.06; 95% CI = - 0.07, - 0.04), insufficient sleeping time (MD = - 0.04; 95% CI = - 0.07, - 0.02), consumption of sugar-sweetened beverage (MD = - 0.02; 95% CI = - 0.03, - 0.01) or fast food intake (MD = - 0.03; 95% CI = - 0.04, - 0.02) reported significantly lower HRQoL scores. When considered additively, each additional lifestyle-related risk factor was associated with an average decrease of 0.03 units (95% CI: - 0.03, - 0.02) CHU9D score. CONCLUSIONS For Chinese students, HRQoL was positively associated with physical activity and sleep duration, but negatively with screen time and consumption of sugar-sweetened beverage and fast food. Moreover, lifestyle-related behaviors may have an additive effect on HRQoL.