Despite increasing interest in understanding the factors influencing awareness and acceptability of the human papillomavirus (HPV) vaccine among Latino parents, to date limited information is available specific to Central American parents living in the United States (US). Therefore, this pilot cross-sectional study was designed to explore and assess Central American immigrant parents’ awareness, acceptability, and willingness to vaccinate their children against HPV, and interest in participating in future HPV-associated cancer prevention study. Fifty-six Central American parents, majority immigrant (96.4%; n = 54) from four countries, El Salvador—50% (n = 27); Guatemala—25.9% (n = 14); Honduras—22.2% (n = 12); and Panama—1.9% (n = 1) participated in this study. Participants completed an interviewer-administered questionnaire survey in their preferred language (i.e., Spanish or English). A little over half of the participants were mothers (57.1%; n = 32) and parents’ mean age was 43.2 years (SD = 6.4). The majority was married or cohabitating (76.8%, n = 43), and 39.3% (n = 22) reported having two children. Seventy-five percent (n = 42) of parents reported they had heard of the HPV vaccine. Fewer fathers were aware of the HPV vaccine (58.3%; n = 14 vs.87.5%, n = 28; p = 0.01) than mothers. Among parents who had heard of the HPV vaccine (n = 42), 85.7% (n = 36) reported their children had received at least one dose of the HPV vaccine. Fewer fathers reported their child had been vaccinated against HPV (64.3%, n = 9 vs. 96.4%, n = 27; p = 0.06) than mothers. Moreover, 90% of parents (n = 18) whose children were unvaccinated reported willingness to vaccinate their adolescent children against HPV if recommended by their child’s physician. Findings indicate parents’ low to moderate awareness of the HPV vaccine, and high willingness to vaccinate their adolescent children if recommended by their child’s physician. Findings also demonstrate fathers’ lower awareness and acceptability of the HPV vaccine than mothers. Despite limitations and the need for more research, findings of this pilot study serve as a valuable first step toward building a knowledge foundation that is needed for developing future studies and interventions targeting Central American immigrant parents living in the US. Future studies can build on the findings of this exploratory study with other research designs and address its limitations by having a larger sample size and accounting for additional factors associated with Central American immigrant parents’ HPV awareness, knowledge, beliefs, attitudes, and vaccine acceptability from other communities across the US.