Background: Social media (Facebook, WhatsApp, Instagram, Twitter) as communication channels have great potential to deliver Human papillomavirus self-test (HPVST) intervention to medically underserved women (MUW) such as women of low income. However, little is known about MUW’s willingness to participate in HPVST intervention delivered through social media. We evaluated factors that contribute to MUW’s intention to participate in the social media-related intervention for HPVST. Methods: A 21-item survey was administered among women receiving food from a local food pantry in a U.S. southern state. Independent variables were social media usage facilitators (including confidentiality, social support, cost, and convenience), and barriers (including misinformation, time-consuming, inefficient, and privacy concerns). Dependent variables included the likelihood of participating in social-driven intervention for HPVST. Both variables were measured on a 5-point scale. We used multinomial logistic regression to analyze the data. Results: A total of 254 women (mean age 48.9 ± 10.7 years) comprising Whites (40%), Hispanics (29%), Blacks (27%), and Other (4%) participated in the study. We found that over 44% of the women were overdue for their pap smears for the past three years, 12% had never had a pap smear, and 34% were not sure if they had had a pap smear. Over 82% reported frequent social media (e.g., Facebook) usage, and 52% reported willingness to participate in social media-driven intervention for HPVST. Women who reported that social media provide privacy (Adjusted Odds Ratio (AOR) = 6.23, 95% CI: 3.56, 10.92), provide social support (AOR = 7.18, 95% CI: 4.03, 12.80), are less costly (AOR = 6.71, 95% CI: 3.80, 11.85), and are convenient (AOR = 6.17, 95% CI: 3.49, 10.92) had significantly increased odds of participating in social media intervention for HPVST. Conclusions: The findings underscore that the majority of the MUW are overdue for cervical cancer screening, regularly use social media, and are willing to participate in social media-driven intervention. Social media could be used to promote HPV self-testing among MUW.