Whenever a discussion on AIDS comes up one cannot escape talking about sexuality issues. Education and communication are currently the only weapons we have against HIV/AIDS. Communication and information can help to fight HIV/AIDS by changing young people’s behaviour through protective education schemes. Communication between parents and their children about sex is often difficult. Although most adults want youth to know about how to prevent HIV and other sexually transmitted infections (STIs), they still have difficulties in communicating about sex. The general objective of this study was to determine factors affecting parents’ participation in adolescents’ home based HIV/AIDS prevention education, in order to provide necessary information to policy makers in order to design more relevant and efficient programmes to combat HIV/AIDS specifically targeting adolescents specifically. The study adopted a cross sectional design using an interview schedule for 120 parents/guardians from ten streets (mitaa) of Musoma Municipality. The Statistical Package for Social Sciences (SPSS) Version 11.5 was used to analyse data. Descriptive statistics were used for identifying cultural, demographic and socio-economic factors affecting parents’ participation in adolescents’ home based HIV/AIDS prevention education. However, prior to this step index scales were developed and used to gauge participation, religiosity and HIV/AIDS awareness. F-test was used to test the hypotheses at 5% level of significance. Key findings indicate that parents’ participation in adolescents’ home based HIV/AIDS prevention education was affected by cultural factors including norms such as feeling shame to discuss with adolescents about sex related issues; lack of knowledge about the technical aspects of HIV/AIDS and sex; as well as adolescents are told issues related to sex when they undergo rite of passage. Values such as adolescents should not know about sex, and open communication leads to children’s loss of respect to elders were revealed. Socio- economic factors such as education level of parents significantly affected their participation in adolescents’ home based HIV/AIDS prevention education. Levels of knowledge about HIV/AIDS were found to be high. Parents’ participation in adolescents’ home based HIV/AIDS prevention education was significantly affected by parents’ religiosity, occupation and level of education, but not affected by type of family, family size, economic status, and HIV/AIDS awareness. The study recommended that the government, and the community respectively should develop policies/programmes and strategies that encourage or involve parents to take part in HIV prevention approaches