Background In the current era of big data, it is critical to address people's demand for health science knowledge. At present, the traditional mode of communicating scientific health knowledge and information technology are interchangeable, resulting in the emergence of a new mode of communicating health science knowledge. To publicize health education and popular science knowledge in a targeted way, to meet the public's needs, and to understand how the public's demand for subjects, contents, and forms of health science service has changed in the epidemic era, the investigation of public's demand for health information and popular science knowledge was conducted. Objective This study aims to understand the differences in demand for health science popularization service providers, contents, channels, forms, and facilities among Chinese citizens with different genders, ages, education levels, economic conditions, and living environments, and to provide reasonable recommendations for developing health science popularization. Methods Questionnaire Star was used to conduct a large sample of random online surveys. In Wuhan, Hubei Province, 2184 questionnaires were issued, 8 invalid questionnaires were eliminated, and 2176 were recovered, with an effective rate of 99.6%. IBM SPSS Statistics 20 was utilized to analyze the survey data. Results (1) In health science popularization service providers selected by the public, the proportion of government departments or government collaboration with other institutions exceeded 73%, indicating that health science popularization services are public goods; (2) access to health science popularization services was lower in township areas than in urban areas (P < 0.001); (3) internet media and communicating with acquaintances, which have the highest popularity rate, were also the two channels that were least trusted by the public; and (4) the differences in contents and service channels of health science popularization among residents with different genders, ages, education levels, economic status, and living environments were statistically significant. Conclusions (1) It is recommended to establish an integrated health science popularization service model with multi-center supply. Government departments, medical institutions, and media should cooperate effectively to provide health science popularization services. (2) The government should pay attention to the fairness of health education and strengthen the supply of health science popularization services in township areas. (3) It is critical to strengthen the public's ability to discriminate network information and pay attention to scientific thinking cultivation. (4) Health science popularization service providers must focus on the differences between public demands and improve the connotation of health science services.