The human papillomavirus (HPV) vaccine is viewed as a critical tool to protect against six HPV-related cancers. Vaccination is recommended from early adolescence through age 26 years. As young people have become increasingly involved in personal health-related decisions, there is a need to tailor HPV vaccine messaging and reach this priority population on social media and digital outlets. TikTok is a growing social media platform with approximately 70% of its users between the ages of 13 and 24 years. The aim of this study was to understand HPV vaccine messaging and interactions on TikTok as a needed first step to identifying effective strategies to reach young people with important health messaging. Content analysis was performed on 170 top TikToks focused on the HPV vaccine. TikToks were assessed for content, classification type, and number of interactions. Most TikToks were provaccine, while antivaccine TikToks had more user interactions. Cancer and prevention were the main content areas of the analyzed provaccine TikToks, while the side effects were the primary focus of antivaccine messages. Approximately 30% of all top TikToks analyzed were developed by health professionals. TikToks without an explicit vaccine opinion primarily described personal experiences and mentioned side effects most often. TikTok is a growing social media platform that can be used to reach young people and encourage HPV vaccine uptake. Health professionals need to consider the interest that users have in personal experiences and address antivaccine narratives related to side effects.