Background: Though human papillomavirus (HPV) vaccination is a safe and effective method of protecting against associated cancers, uptake rates remain low among adolescents. Few studies have examined how social media use contributes to HPV-related knowledge gaps among parents and caregivers. Objective: To investigate the association between social media use and HPV-related awareness and knowledge with a focus on differences by gender and race/ethnicity among a nationally representative sample of adults with children in the household. Methods: We used data from the Health Information National Trends (HINTS) Survey (2017-2019) (N = 2,720). Multivariate logistic regressions were used to examine the association of social media use on HPV awareness and knowledge outcomes. Results: Compared to non-users, engaging in one, two, three, or four social media behaviors were associated with greater HPV awareness (aOR: 2.09; 95%CI: 1.18-3.70, aOR: 2.49; 95%CI: 1.40-4.42, aOR: 2.64; 95%CI: 1.15-6.05, and aOR: 2.44; 95%CI: 1.11-5.36, respectively). Increased social media use was associated with increased HPV vaccine awareness. Men, African American, Hispanic, and Asian American respondents were less likely to be aware of HPV or HPV vaccine. Social media use was not associated with cancer knowledge. Conclusions: Increased social media use is associated with an increased awareness of HPV and HPV vaccine for adults with children in the household. Social media-based efforts can be utilized to increase knowledge of the benefits of HPV vaccination as cancer prevention, which may be a precursor to reducing HPV vaccine hesitancy and encouraging uptake to decrease cancer incidence rates among vulnerable populations.