On February 28, 2023, the Facebook page of the United Nations Children's Fund (UNICEF) South Africa, announced the beginning of the HPV vaccination campaign for 2023. The aim of this study was to examine the attitudes of Facebook users, who commented on the UNICEF South Africa post, towards HPV vaccination to inform the development and implementation of interventions that can increase HPV vaccine acceptance and uptake. Several comments were questions regarding the eligible criteria for vaccination, side effects, consent form, and vaccination strategies. Many Facebook users were hesitant towards HPV vaccination due to various reasons including concerns around side effects, religious beliefs, vaccine stock outs, and their distrust in the institutions or systems involved in vaccination programmes. Few users accepted HPV vaccination because they believed that it was very important thing to do, beneficial for the children’s health, and they have vaccinated they children before. Our findings of the current study contribute to the promotion of acceptance and uptake of HPV vaccination by developing and implementing interventions tailored to address identified barriers that are associated with hesitant to HPV vaccination.