Adolescents are the primary target population for human papillomavirus (HPV) vaccination. The objective of this study is to explore the acceptability of HPV vaccines and evaluate factors related to willingness to be vaccinated among Chinese adolescents.A nation-wide survey was conducted across 14 schools in mainland China. The questionnaire consisted of questions relating to socio-demographic characteristics, knowledge of adolescent sexual health, cervical cancer, HPV and HPV-related disease, and students' willingness to be vaccinated. Chi-square tests and multivariable logistic regression were conducted in the data analysis.A total of 4,062 students participated in this study. Among them, only 17.1% of students reported having heard of HPV vaccines; however, 67.3% were willing to receive the HPV vaccine. Multivariable regression analysis showed that students who were from rural areas, have received sexual health education, have heard of cervical cancer or HPV vaccine, have a positive attitude toward vaccination, reported they were at the risk of developing cervical cancer, and those who value their parents' and teachers' opinions were more willing to receive HPV vaccination.Awareness about the HPV vaccine is low among Chinese adolescents. The factors that most related to willingness to vaccinate among Chinese adolescents were school location, education about vaccination, HPV, and HPV vaccines. Integrating health education on HPV vaccination into existing school-based sexual health curricula may be an effective way to increase HPV vaccination coverage in mainland China.