Background: Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide, with HPV and HPV-related diseases representing a substantial disease burden. HPV vaccination has reduced HPV infections and HPV-related diseases; however, there is growing evidence of delayed or refused vaccination due to a lack of trust in vaccines. Understanding the factors that impact vaccine uptake will allow the development and implementation of successful vaccination programmes. Objectives: This study aimed to evaluate the acceptability of HPV vaccination among adolescents and parents in the United Kingdom (UK). Design: Systematic review. Methods: Online databases (Embase, Medline and Cochrane) and grey literature sources were searched to identify publications pertaining to ‘adolescents’, ‘parents’, ‘vaccine uptake’, ‘vaccine hesitancy’ and ‘barriers or facilitators to vaccination’. Searches were limited to English language and articles published specific to the United Kingdom between 2017 and 2023. Results: Following a review of 152 abstracts, 24 publications met the inclusion criteria. While HPV vaccination is widely accepted in the UK, with coverage reported ⩾80% in peer-reviewed literature, the UK Health Security Agency report that vaccine coverage estimates in England between 2020–2023 remain below 80% and are lower than pre-COVID levels. Several important barriers were identified that may impact vaccine uptake, including system-level (challenges with obtaining consent), psychological/behavioural (perception of HPV risk vs vaccine risks), and sociodemographic factors, with similar factors reported among adolescents and parents. Conclusion: HPV vaccination coverage remains below pre-COVID levels in the UK and common barriers among adolescents and parents have been identified that must be addressed to improve coverage rates. There is currently limited evidence among adolescent boys to fully evaluate any differences in vaccination coverage, or barriers, compared to girls. More research is required into facilitators to vaccination (especially to address sociodemographic barriers), to identify approaches to tackle the barriers that currently impede HPV vaccination uptake.