Little is known about the knowledge and attitudes towards human papillomavirus (HPV) and its vaccines among adolescents in mainland China. Also, limited information has been available on how to improve their knowledge and willingness towards HPV and its vaccines to ensure a successful vaccination program in the future. This was a school-based interventional follow-up study. One urban and one rural junior middle school in Chengdu were selected by convenience sampling. At baseline, half of the grade one students were randomly selected as controls and the rest were interventions. A set of self-administered questionnaires on HPV and its vaccines were completed by both groups at baseline. After that, only the intervention group received a PowerPoint-oriented health education and finished the post-education questionnaires. One year later, both groups completed the same questionnaires as the follow-up survey. In total, 1675 students finished the pre-intervention questionnaires; 751 were from the control group and 924 were from the intervention group. Among them, only 34.3% had heard of cervical cancer/genital warts, while only 15.1% of them had ever heard of HPV. However, 55.2% of students showed their willingness to be vaccinated even before any intervention. Seven variables were found to be associated with the willingness to be vaccinated at baseline. Immediately after the intervention, 88.4% of students were willing to vaccinate themselves. After 1 year, the effectiveness of intervention remained but decreased. Compared with the control group, the intervention group was more aware about cervical cancer, HPV and its vaccines with statistical significance. However, the level of HPV knowledge and willingness to be vaccinated among the intervention group had significantly decreased compared with that immediately after the intervention (P < 0.001). The baseline level of knowledge on HPV, its vaccines, and cervical cancer was very low among junior middle school students in Chengdu, China. However, the willingness to be vaccinated seemed positive. School-based health education is effective and appropriate in increasing the awareness of HPV and willingness towards its vaccines. Regular health education on HPV and cervical cancer prevention at a shorter interval should be guaranteed to ensure continuous effectiveness.