Background: Human Papilloma Virus (HPV) is an important factor in causing many types of cancer, and over 99% of cervical cancers are associated with HPV infection. Although Jiangsu Province has taken the lead in implementing a free HPV vaccination policy, the 17-24 year old population is not covered by the free vaccination, and the vaccination rate is still significantly lower than the international target, with urban-rural differences and cognitive drivers not yet clarified. The aim of this study was to assess the current status of adolescents’ awareness and willingness to vaccinate against HPV in the province and identify key influencing factors. Methods: Multi-stage stratified whole cohort sampling was conducted among 2186 you adolescents in Jiangsu province to describe their HPV-related knowledge and vaccination intentions. A self-administered questionnaire was taken from 1853 students of 6 vocational schools in Huai’an City, Nantong City, Suqian City, Suzhou City and Changzhou City, Jiangsu Province from November 2024 to January 2025 to analyse students’ knowledge of HPV and HPV vaccine, as well as their willingness to be vaccinated against HPV and their influencing factors. Potential categories were analysed to identify different respondents based on their willingness to be vaccinated against HPV. Results: Of the 2186 participants, 281 (12.9%) had been vaccinated against HPV. Of the remaining 1905 questionnaires, 52 invalid questionnaires were excluded, resulting in 1853 valid surveys. Multiple logistic regression analyses showed that enhancing perceived benefits, lowering perceived barriers, strengthening HPV knowledge and education, and developing differentiated strategies for groups such as females and urban dwellers could significantly increase vaccination intentions. Conclusion: The results of this study indicate that although the adolescent population presents a positive attitude towards HPV vaccination, there is still a need to enhance their knowledge of the multiple hazards of HPV through multi-channel education strategies. Simultaneous reproductive health education and vaccine accessibility safeguards provide a scientific basis for advancing the comprehensive prevention and treatment of cervical cancer and the elimination of HPV-related diseases.