Objective: Human papillomavirus (HPV) vaccination rates among Hispanic adolescents in the USA are far below recommended levels. Using a social marketing theory framework, we assessed the four Ps (product, price, place and promotion) as they relate to efforts to promote HPV vaccine initiation. Design: Qualitative study involving in-depth interviews. Setting: A large Southern city in the USA. Method: Eighty-five in-depth qualitative interviews were conducted with Spanish-speaking Hispanic mothers divided into initiated and uninitiated market segments based on whether or not their adolescent child had received the first dose of the HPV vaccine. Data were analysed using directed qualitative content analysis. Results: Results suggest that the desire to prevent illnesses and protect their child drives the decision to vaccinate (product). Most initiated mothers did not experience barriers to vaccination, and market segments described different potential barriers (price). Both marker segments reported that they needed vaccine information before vaccinating (price). Finally, interventions should target clinics, schools and community centres to raise awareness about the importance of vaccinating against HPV (place and promotion). Conclusion: Findings from this formative study can inform the development of an intervention to increase HPV vaccine initiation among Hispanic adolescents.