BACKGROUND: As human papillomavirus (HPV) vaccines become available in developing countries, acceptability studies can help to better understand potential barriers and facilitators of HPV vaccination and guide immunisation programs. METHODS: Prior to a cluster-randomised phase IV trial of HPV vaccination delivery strategies in Mwanza Region, Tanzania, qualitative research was conducted to assess attitudes and knowledge about cervical cancer and HPV, and acceptability of and potential barriers to HPV vaccination of Tanzanian primary schoolgirls. Semi-structured interviews (n=31) and group discussions (n=12) were conducted with a total of 169 respondents (parents, female pupils, teachers, health workers and religious leaders). RESULTS: While participants had heard of cancer in general, most respondents had no knowledge of cervical cancer, HPV, or HPV vaccines. Only health workers had heard of cervical cancer but very few knew its cause or had any awareness about HPV vaccines. After participants were provided with information about cervical cancer and HPV vaccination, the majority stated that they would support HPV vaccination of their daughter to protect them against cervical cancer. Opt-out consent for vaccination was considered acceptable. Most preferred age-based vaccination, saying this would target more girls before sexual debut than class-based vaccination. Potential side effects and infertility concerns were raised by 5/14 of participating male teachers. DISCUSSION: Reported acceptability of HPV vaccination amongst parents, teachers and other community members was high in this population. Respondents stressed the need to provide adequate information about the vaccine to parents, that also addresses side effects and infertility concerns.