Objective: This study aims to estimate the economic burden of disease of outbreak of norovirus gastroenteritis in the Pearl River Delta Region, and provide scientific evidence for the government’s decision-making and control measures. Methods: Using a unified questionnaire, a survey was conducted to the schools and students’ families which had suffered an outbreak of norovirus gastroenteritis in the Pearl River Delta Region from October 2017 to April 2018. Results: The survey found that the mean total economic burden of sick students was 720.41(95%UI=640.45-804.63)RMB. The mean economic burden of sick students who were inpatient, outpatient and self-treatment were 1 712.75(95%UI=328.50-34 00.00), 213.70(95%UI=191.83-236.33) and 58.97(95%UI=43.00-77.69)RMB, respectively. The mean economic burden of transport, extra tutoring and cost of lost labor were 53.63(95%UI=43.98-63.58), 558.49(95%UI=381.40-774.01) and 695.62(95UI=630.25-767.29)RMB. The mean total economic burden of health students was 382.62(95%UI=343.29-424.45)RMB. The mean total economic burden of school was 49 264.53(95%UI=22 363.38-79 976.25)RMB. The total economic burden of disease increases as the level of outbreak increases. The larger the epidemic level, the proportion of sick students’ financial burden gradually decreased, 56.58%,23.27% and 10.93%. Conclusion The high economic burden of disease of norovirus gastroenteritis in the Pearl River Delta Region, respectively, indicating that relevant departments should strengthen the prevention, control and education in order to mitigate the disease economic burden.