To evaluate the quality, reliability, and popularity of YouTube videos addressing retinoblastoma. This was a retrospective, cross-sectional, register-based study. A YouTube search was performed using the keyword retinoblastoma and the first 100 videos that came out were included in the study. Duplicate videos, videos that were not in English, and videos that were less than 1 minute were excluded. The number of views, likes, dislikes, comments, video type (uploaded by physicians, uploaded by public or private institution, uploaded by health channel or uploaded by patients), and country of origin were evaluated for all videos. The popularity of the videos was evaluated with the Video Power Index. The quality of the videos was measured using the DISCERN score (DISCERN), Journal of the American Medical Association (JAMA) benchmark criteria, and Global Quality Score (GQS). Of the 100 videos, 70 videos met the criteria and were included in the study. The mean DISCERN, JAMA, and GQS scores were 42.54 ± 18.77, 2.14 ± 1.03, 2.87 ± 1.42 and 2.99 ± 1.44, respectively. On examining the upload source 18 (25.7%) videos were uploaded by private institutions, 15 (21.4%) videos by physicians, 14 (20.0%) videos by public institutions, 14 (20.0%) videos by health channels, and 9 (12.9%) videos by patients. There was a significant level of agreement between the two commentators evaluating the videos with a power of 91.6% (kappa score: 0.916). Videos uploaded by physicians and public or private institutions had significantly higher DISCERN, JAMA, and GQS scores. The content of YouTube videos regarding retinoblastoma is generally of moderate quality for patients. Increasing the number of videos uploaded by physicians and public or private institutions will increase the quality, reliability, and informative value of the videos. [J Pediatr Ophthalmol Strabismus. 20XX;X(X):XXX-XXX.].