Background: Hong Kong lacks comprehensive school-based sexuality education. Recent public health concerns have brought the inadequacies of sex education in Hong Kong to the forefront. The aim of the proposed study is to develop and evaluate the effectiveness of a comprehensive school-based sexuality education program in Hong Kong.Methods: The proposed study is a prospective longitudinal study implemented in six secondary schools in Hong Kong over two academic years. The study adopts an ecological approach providing informational workshops for students, teachers and school management, social workers and guidance counsellors and parents. Study outcomes will be evaluated through pre- and post-tests.Results: Key outcomes of interest among students include sexual health knowledge, awareness of values motivating healthy sexual decisions, understanding and efficacy of sexual communication and intention to use contraception. Among school employees and parents key outcomes include self-efficacy to engage in sexual health discussions with students/children, sexual health knowledge and awareness of Hong Kong community sexual health resources.Conclusions: The proposed study will result in the development of a tested school-based culturally relevant comprehensive sexual health education program. Ultimately, this program aims to not only empower adolescents and their trusted adults in building a supportive environment for sexual health promotion but also construct a learning network to generate longitudinal evidence for the effectiveness of comprehensive sexuality education in improving sexual health outcomes. The program has the potential for expansion through widespread adoption in Hong Kong schools to benefit more adolescents and reduce the medical and societal burdens related to crisis pregnancy, sexually transmitted infections and sexual abuse. Copyright © 2021 BioMed Central.