© Peishan Ning, Deyue Gao, Peixia Cheng, David C Schwebel, Xiang Wei, Liheng Tan, Wangxin Xiao, Jieyi He, Yanhong Fu, Bo Chen, Yang Yang, Jing Deng, Yue Wu, Renhe Yu, Shukun Li, Guoqing Hu. Background: With the growing popularity of mobile health technology, app-based interventions delivered by smartphone have become an increasingly important strategy toward injury prevention. Objective: This study aimed to develop a framework supporting the design of an app-based intervention to prevent unintentional injury, targeted for caregivers of Chinese children aged 0 to 6 years. Methods: A theory-based mixed-method study, including focus groups and Web-based quantitative survey, was performed. Adult caregivers who care for children aged 0 to 6 years and own a smartphone were recruited into 2 sequential stages of research. First, focus groups were conducted among the caregivers at community health care centers and preschools from December 2015 to March 2016. Focus groups (8-10 participants per group) explored awareness, experiences, and opinions of caregivers toward using an app to prevent unintentional injury among children. Second, based on the focus groups findings, a Web-based quantitative survey was designed and distributed to caregivers in November 2016; it collected information on specific needs for the app-based intervention. Thematic analysis and quantitative descriptive analyses were performed. Results: In total, 12 focus groups were completed, involving 108 caregivers. Most participants expressed a strong desire to learn knowledge and skills about unintentional child injury prevention and held positive attitudes toward app-based interventions. Participants expressed multiple preferences concerning the app-based intervention, including their contents, functions, interactive styles, installation and registration logistics, and privacy protection and information security. Following the focus groups, 1505 caregivers completed a WeChat-based quantitative survey, which generated roughly similar results to those of focus groups and added numerical metrics concerning participants’ preferences on what to learn, when to learn it, and how to learn it. A detailed framework was established involving 5 components: (1) content design, (2) functional design, (3) interactive style, (4) installation and registration logistics, and (5) privacy protection and information security, and 15 specific requirements. Conclusions: We developed a framework that can be used as a guide to design app-based interventions for parents and caregivers, specifically for unintentional injury prevention of children aged 0 to 6 years.