Background: The disease burden of seasonal influenza is substantial in China, while there lacks nation-wide economic burden estimates. This study aims to examine influenza-like illness (ILI) prevalence, healthcare seeking behaviors, economic impact of ILI and its influencing factors among children, chronic disease patients and the elderly during the 2018–19 influenza season. Methods: From August to October 2019, 6668 children’s caregivers, 1735 chronic disease patients, and 3849 elderly people were recruited from ten provinces in China to participate in an on-site survey. The economic burden of ILI consisted of direct (medical or non-medical) and indirect burden, and multivariate linear regression was adopted to predict the influencing factors of total economic burden. Results: There were 45.73% children, 16.77% chronic disease patients and 12.70% elderly people reporting ILI, and most participants chose “Outpatient service only”, “Over-the-counter (OTC) medication only” or “Outpatient + OTC” after ILI. The average total economic burden of ILI was 1848 yuan (USD266.1) for children, 1105 yuan (USD159.1) for chronic disease patients and 2064 yuan (USD297.2) for the elderly. Multivariate linear regression showed that boys, the only child in family, and urban adult residents tended to have larger economic burden after ILI. Conclusions: Large economic burden of ILI was highlighted, especially among the elderly with less income and larger medical burden, as well as children with higher prevalence and higher self-payment ratio. It is important to adopt targeted interventions for high-risk groups, and this study can help national-level decision-making on the introduction of influenza vaccination as public health project.