Objective: This study aims to investigate the impact of individual and family factors on anxiety and loneliness of middle school students during quarantine in the COVID-19 pandemic and to provide reference for discussing the possible effective intervention paths in the stress process of public health emergencies. Methods: A total of 11 596 students from junior and high schools in Shanghai were selected to complete the questionnaire with the stratified random cluster sampling method. Generalized Anxiety Disorder(GAD-7) and UCLA Loneliness Scale, University of California at Los Angeles(ULS-6) were used for the survey. Results: The prevalence of anxiety and loneliness were 34.78% and 52.44% respectively. The rate of anxiety and loneliness in girls (36.13%, 54.62%) was higher than that of boys (33.44%, 50.28%)(χ 2=17.03, 21.82, P<0.05). Logistic regression analysis showed that graduates (OR=1.34, 95%CI=1.18-1.52), students ranking in the middle (OR=1.25, 95%CI=1.08-1.45) or in the bottom 25% (OR=1.76, 95%CI=1.50-2.05), non only children in the family (OR=1.25, 95%CI=1.09-1.43) and low socioeconomic status (OR=1.42, 95%CI=1.23-1.65) were associated with increased risk of moderate and severe level of anxiety(P<0.05). Girls(OR=1.20, 95%CI=1.12-1.30), graduates(OR=1.13, 95%CI=1.04-1.24), non residents(OR=1.20, 95%CI=1.09-1.33), lower level of grades(OR=1.72, 95%CI=1.55-1.91) and not living with parents(OR=1.32, 95%CI=1.18-1.48) were associated with increased risk of loneliness(P<0.05). Conclusion During the quarantine period caused by the COVID-19 pandemic, negative emotions such as anxiety and loneliness among adolescents need attention, especially females, graduates, only children and students with low rankings or low socioeconomic status.