Background: Almost all cases of cervical and anal cancer have been linked to the human papillomavirus (HPV). However, in addition to women who develop HPV-related cervical cancer, both men and women can also develop cancers of the anus, oral cavity, and oropharynx that are attributed to HPV. However, literature on HPV vaccination among boys globally, in Africa, and most especially in Ghana is scarce. Thus, the main objective of this study was to explore the acceptance of HPV vaccination in boys among mothers from selected churches in Accra, Ghana. Methods: In this study, a qualitative exploratory design was utilized to enlist 30 mothers who have male children aged between 9 and 12 years from the Greater Accra Region of Ghana. The recruitment of participants was carried out using a purposive sampling technique, and they were subsequently interviewed in-depth in a face-to-face setting, with the entire conversation being recorded for reference. After transcription, the recorded data were analyzed through content analysis. Findings: Upon analyzing the data, two (2) primary themes and 11 sub-themes emerged. The research showed that although the majority of the mothers were unaware of HPV in boys, they perceived it as a positive initiative and expressed a willingness to allow their sons to receive the vaccine. However, some participants mentioned certain factors that they believed could hinder the acceptance of HPV vaccination in boys among mothers. These included concerns about injection-related pain, high cost, and fears that the vaccine could make men immoral or infertile. Conclusion: The study revealed poor awareness of HPV vaccination in boys among mothers, and hence, suggested the need to increase the awareness on HPV vaccination in boys among mothers as well as the public to increase its acceptance.