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Sub-Saharan Africa carries a high burden of the HIV epidemic, with young adults being particularly affected. Well-designed school-based HIV prevention interventions can contribute to establishing protective behaviour. The aim of this study was to explore the needs of primary school students and teachers in the region of Kagera, Tanzania, regarding an HIV prevention intervention in the primary school setting. The needs assessment was structured according to the PRECEDE component of the PRECEDE-PROCEED model. Qualitative data was collected in six focus group discussions with primary school students and teachers. Key informant interviews with seven experts were conducted. We employed qualitative content analysis to analyse data in MAXQDA. The findings suggest that teachers need to be adequately trained to provide HIV and sex education and to support HIV-positive students. Enabling structural factors, such as an appropriate syllabus, are required. Stigmatization has been reported a major barrier to HIV prevention in schools. Teachers and students identified a more trustful relationship between each other as well as to legal guardians of children as a basis for HIV prevention. These findings will inform the development of a tailored HIV prevention intervention.