As the age of initiating sexual intercourse has gradually decreased among South Korean adolescents, earlier vaccination of adolescents for human papillomavirus (HPV) is necessary before their exposure to HPV. Health communication includes "cues to action" that lead to preventive health behaviors, and recently, social networking services, which operate with fewer time and space constraints, have been used in various studies as a form of eHealth communication. This study aims to investigate the feasibility and usability of an eHealth communication intervention for HPV vaccination in middle-school girls aimed at the girls and their mothers. The eHealth communication intervention for HPV vaccination was developed using a 6-step intervention mapping process: needs assessments, setting program outcomes, selection of a theory-based method and practical strategies, development of the intervention, implementation plan, and testing the validity of the intervention. A review of 10 studies identified effective health communication messages, delivery methods, and theories for HPV vaccination among adolescents. Barriers including low knowledge, perceived threat, and the inconvenience of taking 2 doses of the vaccine were identified through focus groups, suggesting a need for youth-friendly and easy-to-understand information for adolescents delivered via mobile phones. The expected outcomes and the performance objectives are specifically tailored to reflect the vaccination intention. Behavior change techniques were applied using trusted sources and a health belief model. Health messages delivered through a KakaoTalk chatbot improved awareness and self-efficacy. Quality control was ensured with the use of a log system. The experts' chatbot usability average score was 80.13 (SD 8.15) and the average score of girls was 84.06 (SD 7.61). Future studies need to verify the effectiveness of health communication strategies in promoting HPV vaccination and the effectiveness of scientific intervention using a chatbot as a delivery method for the intervention.