Health promotion and disease prevention are crucial for improving public health and alleviating the burden of illness in the population. This study aimed to investigate, the sources of health information most used and trusted, and the health topics most searched, by means of a nationwide cross-sectional online survey of a representative sample of the adult Swiss general population. Overall, complete surveys of 2020 participants were analysed (mean age 47 years old, 51% male, and matching the Swiss population regarding age, sex, and language-speaking region). Sources' use were calculated with descriptive statistics per sex and age groups. The most frequently used sources were general practitioners (min: 46% to max: 73%), government websites (40% to 55%), family and friends (37% to 63%), pharmacy (33% to 46%), and television (21% to 57%). The most trusted sources were specialised physicians (94% to 98%) general practitioners (90% to 96%), and pharmacies (81% to 89%). Based on multivariable controlled regression, age (per five years increase) was associated with increased odds of using television (Odds Ratio (OR): 1.19, 95% Confidence Interval (CI): 1.12 to 1.21), print media (OR: 1.15, 95% CI: 1.10 to 1.19), radio (OR: 1.15, 95%CI: 1.10 to 1.20), and the general practitioner (OR: 1.11, 95% CI: 1.07 to 1.15), and decreased odds of using news websites (OR: 0.94, 95% CI:0.9 to 0.98), family and friends (OR: 0.93, 95% CI: 0.9 to 0.98), foreign authorities websites (OR: 0.91, 95%CI: 0.86 to 0.97), and social media (OR: 0.88, 95% CI: 0.84 to 0.92). Women were more likely to seek health information in the pharmacy (OR: 1.39, 95% CI: 1.15 to 1.68), specialised physicians (OR: 1.39, 95% CI:1.13 to 1.72), television (OR: 1.41, 95% CI: 1.16 to 1.72), and books (OR: 1.9, 95% CI: 1.44 to 2.5). The most searched health topics, based on the International Classification of Primary Care, 2nd edition (ICPC2), were general and unspecified symptoms (20.9%) and musculoskeletal issues (19.4%). The use of these findings by policymakers and health care providers could potentially enhance the effectiveness of health-related education strategies, by aligning communication efforts with the populations' preferences and content needs, and allocating resources where they are most commonly accessed and trusted, namely in the general practice.