Background: It has been proven that vaccination is effective against Human Papillomavirus (HPV) infections, genital warts, and pre-cancerous and cancerous cervical lesions. Nevertheless, the HPV vaccine coverage of 37.4 % in 2021 in France is one of the lowest in Europe. To explore and understand the reason why French population is so late compared to its neighbours, we carried out focus groups with mothers and with National Education school staff. We aimed to identify knowledge and perceptions of HPV in both study populations, as well as factors influencing HPV vaccination. Methods: Between January 2020 and March 2021, we performed a qualitative study using an inductive approach with a thematic content analysis (TCA). We conducted semi-structured focus groups with 29 people including 15 mothers of adolescents in middle schools and 14 school staff from the national education system. Results: Different factors influenced the decision-making process of parents and school staff: knowledge and perceptions of HPV and its vaccine, sources of information about HPV and vaccination. Mothers’ discourses differed from those of school staff. They mentioned the importance of gynaecological monitoring and the negative image of pharmaceutical companies, and questioned internet as a reliable source of information. For their part, school staff mentioned cultural and/or religious affiliation, municipalities’ role to inform the population, and ethical dilemma or logistical challenges regarding HPV vaccination in schools. Conclusion: The results of these focus groups provided information on which elements may harm or help HPV vaccination. Identified perceptions, beliefs, knowledge, barriers, and facilitators will help us to build an intervention program focus on general practitioners (GP), school staff, parents, and adolescents.