Objective: To understand the knowledge and behavior towards COVID-19 among primary and middle school students in Guangdong province, so as to provide basis for health education on epidemic prevention and control. Methods: An online questionnaire survey was conducted among 1 222 403 primary and middle school students in Guangdong Province from March 8 to 31, 2020. Results: In Guangdong Province, 96.28%, 80.01% and 38.58% of primary and middle school students knew the transmission route of the novel coronavirus was droplet transmission, contact transmission and aerosol transmission respectively, and 78.22% of the students knew the two main transmission routes. Among COVID-19 prevention and control measures, the top three well-known measures were mask wearing(99.69%), frequent hand washing(99.06%) and social distancing(96.21%). During the pandemic, 88.48% of students wore masks every time they went out, 32.15% reported that they needed parental supervision, and 53.97% reported they would continue wearing masks after the pandemic. 87.21% of students washed their hands every time after going out, 18.78% reported that they needed parental supervision, and 94.92% reported that they would continue washing their hands frequently after the pandemic. Conclusion Primary and middle school students in Guangdong Province had high rates of awareness on transmission route and prevention and control measures of COVID-19. During the pandemic, the rates of wearing masks or washing hands every time after going out was high, and the rates of behavior intention of washing hands after the pandemic was high.