In the process of advancing the development of a Healthy China，it is of great significance to explore the key factors and configuration paths influencing the dissemination effectiveness of health science popularization short videos on TikTok. This study，based on the socio-technical systems theoretical framework and the fsQCA method，analyzes the complex relationships between key factors in the“social”and“technical”sub-system dimensions and the achievement of high dissemination effectiveness of health science popularization short videos from a configurational perspective. The findings show that：(1) Individual key factors are not necessary conditions for achieving high dissemination effectiveness. However，conditional variables such as topic guidance and content related to healthy lifestyles play a more universally significant role in attaining high dissemination effectiveness for short videos. (2) Three types of configuration paths can achieve high dissemination effectiveness：socially-driven，technologically-driven，and“subject-title-length”compensatory paths. In addition，this study identifies four configurations leading to low dissemination effectiveness. First，shorter titles and video durations result in insufficient depth in the video's content. Secondly，the lack of appeal in the video content categories and themes results in low dissemination effectiveness. Thirdly，the absence of topic guidance and content categorization leads to low dissemination effectiveness. Lastly，the uncertainty of key elements such as title length and video duration within the technical system can also lead to low dissemination effectiveness. This paper adopts a configurational analysis perspective to examine the coupling effects between key factors on the dissemination effectiveness of health science popularization short videos. The findings hold significant theoretical and practical value in uncovering the configurational paths for achieving high dissemination effectiveness in such videos.