Background <p>Social media has become a significant platform for health knowledge popularization worldwide, especially during public health crises. However, the factors influencing healthcare professionals’ intention to engage in health knowledge popularization on social media, particularly in China, remain underexplored due to the unique socio-medical environment.</p> Objective <p>This study examines determinants of Chinese healthcare professionals’ social media-based health knowledge popularization participation, evaluating the applicability of the Unified Theory of Acceptance and Use of Technology (UTAUT) and Perceived Risk Theory.</p> Methods <p>We developed a survey integrating UTAUT constructs (performance expectancy, effort expectancy, social influence, facilitating conditions) with perceived risk. Data from 762 professionals across four Shanghai tertiary hospitals were analyzed using structural equation modeling.</p> Results <p>Social influence (β = 0.299, <i>p</i> &lt; 0.001), performance expectancy (β = 0.221, <i>p</i> &lt; 0.001), and effort expectancy (β = 0.312, <i>p</i> &lt; 0.001) significantly positively predicted participation intention. Facilitating conditions directly affected actual behavior (β = 0.079, <i>p</i> &lt; 0.05), while perceived risk showed no significant association with intention (β=-0.019, <i>p</i> = 0.581).</p> Conclusions <p>Institutional support emerges as crucial in mediating healthcare professionals’ social media engagement, with social influence and anticipated effectiveness being primary motivators. The non-significant role of perceived risk may reflect China’s performance evaluation systems and policy safeguards mitigating professional concerns. Practical implications suggest that enhancing organizational support through resource allocation and workload adjustments could effectively promote online health knowledge popularization participation.</p> Clinical trail number <p>Not applicable.</p>