Background The northeastern region of Argentina has the highest age-adjusted cervical cancer mortality rates. Given the strong link between HPV infections and cervical cancer, one of the main interventions is the population-based use of HPV vaccines. However, the acceptability is not very clear in low- and middle-income countries. The purpose of this study was to estimate the level of HPV vaccine acceptance and associated determinants among caregivers of girls in a northeastern city of Argentina. Methods A school-based survey was conducted in 2015 using a multistage sampling method. The primary sample unit were schools stratified by socioeconomic status selected at random, and caregivers of school girls were interviewed. The acceptability was determined using the adapted Theory of Planned Behavior. We performed logistic regression models to assess associated determinants. Results The study included 347 caregivers. The intention to vaccinate was 59.88%. A positive attitude of caregivers (aOR 4.67; 3.11–7.03) and positive influence of social norms (aOR 1.95; 1.03–3.70) were the main predictors independently associated to the intention to vaccinate against HPV. In contrast, practicing a Christian non-Catholic religion decreased the intention to vaccinate against HPV (OR 0.59; 0.36–0.95). All other factors evaluated were not significantly associated with intention to vaccinate against HPV. Conclusions This study shows that evaluating attitudes, normative social beliefs, and perceived self-efficacy regarding HPV vaccination can be of utmost importance for mapping and planning of health-related strategies in developing countries.