Given the need to improve patient knowledge about HPV-related oral lesions, awareness of HPV infection prevention measures, and compliance with vaccination, as well as patient demand for free and easy access to well-tailored and time-saving health information, the present cross-sectional study examined the accuracy of relevant YouTube videos and their suitability for mass-reach health communication and HPV vaccination promotion. A video search was performed, using keywords obtained from the Google Trends website, until 9 January 2023. Video selection and data collection were performed by independent, pre-calibrated examiners. Descriptive statistics were performed on videos’ general characteristics, source reliability, popularity, information and quality, content topics, vaccination-encouraging/discouraging messages, and educational value. Pearson’s correlation was calculated between educational value and all parameters. Mann–Whitney U test compared very low/low vs. medium/good/excellent educational value and HPV vaccination-encouraging vs. -discouraging videos. Most of the 97 YouTube videos analyzed were moderately accurate and reliable, 53% had moderate/good/excellent educational value, and 80% encouraged HPV vaccination, making them suitable for mass-reach communication. The limited role of oral healthcare providers in uploading relevant content, with the poor dissemination of information about HPV-related benign and malignant oral lesions, may be expanded by purposefully using YouTube and other mass media to improve patient knowledge of HPV-related oral lesions and promote HPV vaccination, which also underscores its potential beneficial oral effects.