Human papillomavirus (HPV) vaccine offers protection of between 80 and 100% for anogenital warts and 60-80% in reducing the incidence of pre-malignant lesions from cervical cancer. However, uptake remains low in Nigeria among adolescent girls. This study was a qualitative study that assessed mothers' acceptability and concerns regarding uptake of HPV vaccine by their adolescent daughters. In-depth interviews were conducted with 20 mothers of adolescents girls aged 9-15 years. A snowballing sampling technique was adopted to select the mothers within the community. Consent was obtained for the use of audiotapes, which were transcribed verbatim with thematic analysis of data. Mothers were between the ages of 30-49 years and most of them were traders. Almost all of the women have heard about cervical cancer, but their knowledge about cervical cancer and HPV vaccine was low. Despite their low knowledge, most of the mothers accepted that the vaccine is good and was willing for their adolescent daughters to take the HPV vaccine for the prevention of HPV. However, cost of the vaccine, side effects, and potential exposure of their daughters to promiscuity after taking the vaccine for protection were the major concerns expressed by the mothers as regards to HPV vaccine uptake by their daughters. Findings highlight the need for health promotion and education programs about cervical cancer, HPV, and HPV vaccine to increase awareness and knowledge among mothers of adolescent girls. Also, HPV vaccination should be included as part of routine immunization for female adolescents.