Objective Despite the fact that the human papillomavirus vaccine (HPVV) has been approved in mainland China since 2016, there is a lack of inoculation among Chinese college women. This multi-center, online interventional RCT based on the information-motivation-behavioral skills (IMB) model intended to investigate if the intervention may improve human papillomavirus vaccine acceptance and awareness among target women. Methods Participants were selected from comprehensive universities and allocated to 1 of 2 groups: intervention or control. After the baseline survey, participants in the intervention group were given 10-minute online IMB model-based education every day for 7 days. Self-administered questionnaire surveys on Human papillomavirus knowledge, HPVV acceptability, and IMB construct toward HPV vaccination were performed at pre- and post-intervention. Results The baseline survey was completed by 3739 female university students from the intervention (n = 1936) and control groups (n = 1803) between February and April 2020. The average score of students on 11 HPV-related questions was 5.225 ± 2.739, and only 32.07% (1199/3739) of them showed a willingness to be vaccinated against HPV. After the intervention, the intervention group had a higher willingness to vaccinate themselves and encourage their friends to get the HPVV compared to the control group (40.39% vs 31.56%, 82.67 vs 73.18%, P < .001), and the difference in knowledge scores between the 2 groups was significant (7.917 ± 1.840 vs 5.590 ± 2.859, P < .001). In addition, 8 students in the intervention group self-reported receiving HPVV during the research period. Conclusions This IMB model-based intervention showed positive effects on the participants’ knowledge, motivation, and perceived objective skills toward HPV vaccination and has the potential to improve the vaccination among Chinese college women.