Background Social media provide a window onto the circulation of ideas in everyday folk psychiatry, revealing the themes and issues discussed both by the public and by various scientific communities. Objective This study explores the trends in health information about autism spectrum disorder within popular and scientific communities through the systematic semantic exploration of big data gathered from Twitter and PubMed. Methods First, we performed a natural language processing by text-mining analysis and with unsupervised (machine learning) topic modeling on a sample of the last 10,000 tweets in English posted with the term #autism (January 2021). We built a network of words to visualize the main dimensions representing these data. Second, we performed precisely the same analysis with all the articles using the term “autism” in PubMed without time restriction. Lastly, we compared the results of the 2 databases. Results We retrieved 121,556 terms related to autism in 10,000 tweets and 5.7x109 terms in 57,121 biomedical scientific articles. The 4 main dimensions extracted from Twitter were as follows: integration and social support, understanding and mental health, child welfare, and daily challenges and difficulties. The 4 main dimensions extracted from PubMed were as follows: diagnostic and skills, research challenges, clinical and therapeutical challenges, and neuropsychology and behavior. Conclusions This study provides the first systematic and rigorous comparison between 2 corpora of interests, in terms of lay representations and scientific research, regarding the significant increase in information available on autism spectrum disorder and of the difficulty to connect fragments of knowledge from the general population. The results suggest a clear distinction between the focus of topics used in the social media and that of scientific communities. This distinction highlights the importance of knowledge mobilization and exchange to better align research priorities with personal concerns and to address dimensions of well-being, adaptation, and resilience. Health care professionals and researchers can use these dimensions as a framework in their consultations to engage in discussions on issues that matter to beneficiaries and develop clinical approaches and research policies in line with these interests. Finally, our study can inform policy makers on the health and social needs and concerns of individuals with autism and their caregivers, especially to define health indicators based on important issues for beneficiaries.