<p dir="ltr">Cervical cancer remains a significant global public health threat, particularly in low- and middle-income countries, like Ethiopia. The Human Papillomavirus (HPV) vaccination is the most effective tool to prevent HPV transmission and reduce cervical cancer-related mortality, but the vaccine uptake remains suboptimal. The public perception of the HPV vaccine is marked by fear and doubt. Although girls are the primary targets of HPV vaccination, little is known about their perspectives, especially in low- and middle-income countries (LMICs). This study addressed the research question: How do adolescent girls perceive the HPV vaccine, and what factors influence their confidence and uptake? The aim was to explore girls’ perceptions and to identify the challenges and factors that shape girls HPV vaccine confidence and uptake. This is a qualitative study that used eight 30 minutes focus group discussions (FGD) with 9 to 10 girls each for a total of 76 girls aged 12 to 15 from selected schools in Addis Ababa. Three trained researchers facilitated the discussion. From using reflexive thematic analysis (RTA), four key themes were created. The FGDs revealed that rumors, misinformation, and poor communication fueled girls’ fear and limited their engagement in the vaccination campaign. Their decisions were influenced by parents, peers, and prior COVID-19 vaccination experiences, while minimal involvement hindered awareness and informed choices. In conclusion, the study underscored the importance of effective communication and involving girls in vaccination campaigns to reduce misinformation, improve awareness, and increase vaccine uptake.</p>