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ObjectiveTo investigate the knowledge and influencing factors of willingness to receive human papillomavirus (HPV) vaccination among senior primary school students in Guangdong province, and to provide a reference for relevant departments to formulate policies. MethodsUsing stratified multistage cluster sampling and a self-developed questionnaire, 1 610 students in grades 5 and 6 from 7 primary schools in the Pearl River Delta region, eastern, western, and northern regions of Guangdong province were selected to participate in a self-administered, on-site, anonymous survey from June to October 2022. The students′ awareness of HPV, knowledge of HPV vaccination, willingness to receive HPV vaccination, and factors influencing willingness to receive HPV vaccination were analyzed.ResultsFor a total of 1 314 participants with valid responses, the HPV awareness and HPV vaccine knowledge rates were 61.49% and 66.13%, respectively, and the HPV vaccine uptake rate was 74.73%. Multivariate logistic regression analysis showed that participants who were female (odds ratio [OR] = 2.15, 95% confidence interval [95%CI]: 1.60 – 2.80), lived in an urban area (OR = 1.56, 95%CI: 1.20 – 2.02), and from the Pearl River Delta region (OR = 3.64, 95%CI: 2.28 – 5.81) and the northern region of the province (OR = 5.65, 95%CI: 4.00 – 7.97) were more likely to have heard of HPV, and the participants were female (OR = 2.11, 95%CI: 1.60 – 2.78), lived in an urban area (OR = 1.45, 95%CI: 1.11 – 1.89), and from the Pearl River Delta region (OR = 5.20, 95%CI: 3.06 – 8.83) and the northern region of the province (OR = 6.30, 95%CI: 4.39 – 9.06) were more likely to have heard of HPV vaccine; the results also showed that the participants who were female (OR = 7.07, 95%CI: 4.89 – 10.21), had heard of HPV (OR = 1.94, 95%CI: 1.29 – 2.93), and were aware of HPV vaccine (OR = 1.65, 95%CI: 1.07 – 2.55) were more likely to be willing to receive HPV vaccination. ConclusionAwareness of HPV and knowledge of HPV vaccine are not high among senior primary school students in Guangdong province, but willingness to receive HPV vaccination is relatively high. Residential area, living region and gender are the main factors influencing HPV awareness and HPV vaccine knowledge and willingness to receive HPV vaccination among the students.