Background In France, human papillomavirus (HPV) vaccination coverage is low, with only 30.7% of 17-year-old girls having received a complete HPV vaccination schedule in 2020. Aim The aim of this study is to determine the perspective and behaviors of general practitioners (GPs) regarding HPV vaccination with their patients and to identify if a reluctance is observed. Design and Setting This qualitative study is based on semi-directed individual interviews conducted between December 2019 and December 2020. A representative sample of GPs with various profiles was included from four French regions. Method A purposive sampling method was employed, and interviews continued until data saturation was reached. The analysis was based on grounded theory. Results Twenty-six GPs aged 29–66 years were interviewed. The measures taken by the French health authorities (lowering the target age, reimbursing the vaccine, extending the target population to boys) were perceived as facilitators. Reported barriers included organizational challenges due to low attendance of adolescents, and relational barriers primarily due to parental vaccine hesitancy. Physicians had to address fears regarding perceived risks and concerns about sexuality associated with HPV vaccination, which were linked to the socio-cultural characteristics of families. Physicians developed strategies including mobilizing scientific knowledge, empowering families by promoting health through prevention, repetition of vaccination proposals, personal experience, and relationship. Different practices were identified according to three GP typologies: effective, convinced but unpersuasive, and reluctant physicians. Conclusion Based on these results, specific interventions, including communication techniques, especially for hesitant or unpersuasive physicians, are needed to enable GPs to become more effective.