Objective: To understand the impact of social media usage on the human papilloma virus(HPV) vaccination willingness among college students in Xinjiang, so as to provide a theoretical basis for early prevention of HPVrelated diseases and preventive education. Methods: From March to April 2022, a total of 834 college students were selected from three universities including Xinjiang Agricultural University, Xinjiang Normal University and Xinjiang Medical University by stratified cluster random sampling method for online and offline surveys. The demographic characteristics, social media usage, risk perception, HPV vaccination willingness were obtained through questionnaires, and the Logistic regression analysis method was used to explore the role of HPV vaccine risk perception between social media use and HPV vaccination willingness of college students. Results: Associations were found between social media use (contact intensity, satisfaction, trust), risk perception (risk perception disorder, risk perception benefit) and HPV vaccination willingness among college students (r=0.37, 0.34, 0.35; 0.25, 0.31, P<0.05). Risk perception benefit had an intermediary effect between social media contact intensity, social media satisfaction, social media trust and HPV vaccination willingness, and the intermediary effects were 0.03 (95%CI=0. 01-0.06), 0.04(95%CI=0.02-0.07), 0.04(95%CI=0.01-0.06),and the proportions of intermediary effect were 18.00%, 26.35%, 23.00%, respectively.Risk perception disorder had an intermediary effect between social media satisfaction and HPV vaccination willingness [0.02 (95%CI=0.00-0.04)], and the intermediary effect accounts for 11.36%. Conclusions Risk perception benefit is the most important related factors of HPV vaccine willingness, which plays an intermediary effect between social media usage and the willingness to HPV vaccination. HPV publicity and education should be strengthened on social media platforms to promote HPVrelated knowledge and awareness of active prevention of HPV infection among college students.