BACKGROUND: As the Internet becomes an increasingly vital source of medical information, the quality and reliability of brain tumor-related short videos on platforms such as TikTok and Bilibili have not been adequately evaluated. Therefore, this study aims to assess these aspects and explore the factors influencing the dissemination of such videos. METHODS: A cross-sectional analysis was conducted on the top 100 brain tumor-related short videos from TikTok and Bilibili. The videos were evaluated using the Global Quality Score and the DISCERN reliability instrument. An eXtreme Gradient Boosting algorithm was utilized to predict dissemination outcomes. The videos were also categorized by content type and uploader. RESULTS: TikTok videos scored relatively higher on both the Global Quality Score (median 2, interquartile range [2, 3] on TikTok vs. median 2, interquartile range [1, 2] on Bilibili,  = 1.51E-04) and the DISCERN reliability instrument (median 15, interquartile range [13, 18.25] on TikTok vs. 13.5, interquartile range [11, 16] on Bilibili,  = 1.66E-04). Subgroup analysis revealed that videos uploaded by professional individuals and institutions had higher quality and reliability compared to those uploaded by non-professional entities. Videos focusing on disease knowledge exhibited the highest quality and reliability compared to other content types. The number of followers emerged as the most important variable in our dissemination prediction model. CONCLUSION: The overall quality and reliability of brain tumor-related short videos on TikTok and Bilibili were unsatisfactory and did not significantly influence video dissemination. Future research should expand the scope to better understand the factors driving the dissemination of medical-themed videos.