AimTo examine relationships between hypothesized potential predictors of vaccination and adolescent's Human papillomavirus (HPV) vaccination intention and whether these predictors differed by sex. We also investigated adolescents' experiences and preferences regarding learning about HPV through social media and other technology, to inform future tailored interventions.DesignCross‐sectional research design.Methods119 adolescents ages 11–17 years who had not received any HPV vaccine were enrolled. Purposive sampling was used to recruit participants from community and clinical settings, with the majority of households located in economically disadvantaged neighbourhoods in a southwest state. Participants completed an anonymous survey. Descriptive statistics, independent t‐tests, chi‐square test and hierarchical logistic regression were conducted to describe the sample, examine relationships between potential predictors and HPV vaccination intention and investigate sex differences.ResultsThe mean sample age was 13.76 years (SD = 2.03); 63% female; 42% Hispanic/Latino; 55.5% received free or reduced‐price lunch. Compared to White adolescents, Hispanic/Latino adolescents reported higher HPV vaccination intention (AOR = 24.10, CI 95% [3.85–150.82]; p < 0.001). Adolescents who had higher perceived risk of contracting HPV (AOR = 1.89, CI 95% [1.23–2.91]; p = 0.004) and perceived more facilitators (AOR = 1.61, CI 95% [1.22–2.12]; p < 0.001) reported higher HPV vaccination intention. Compared to boys, girls (AOR = 0.28, CI 95% [0.08–0.97]; p = 0.045) had lower HPV vaccination intention. Adolescents also showed strong interest in learning HPV‐related issues through digital education.ConclusionAdolescent HPV vaccination rates in the United States are significantly below the targeted 80% completion goal. Nurses play a critical role in protecting adolescents from HPV infection and related cancers. Digital interventions addressing HPV vaccine‐related risks and facilitators and engaging key personnel (adolescent, parent, healthcare provider, teacher) in different settings have the potential to increase adolescent's vaccination intention.No Patient or Public Contribution to This StudyPatients or the general public were not involved in the design, analysis or interpretation of the data in this study.