Background: Human papillomavirus (HPV) DNA testing has been shown to be an effective approach to cervical cancer screening, and self-collection sampling for HPV testing could be a potential alternative to Pap test, provided that women who tested positive by any method get timely follow-up and care. This feasibility study examined acceptability and usability of self-collected sampling for HPV testing among African-American (AA) women in the Mississippi Delta to inform the development of interventions to promote cervical cancer screening in this population. Methods: The study consisted of two phases. Phase I consisted of eight focus groups (n = 87) with AA women to explore knowledge, attitudes, and beliefs about cervical cancer and HPV infection as well as acceptability of self-collected sampling for HPV testing. In phase II, we examined the usability of this technology through one discussion group (n = 9). The Health Belief Model guided data collection and analysis. Results: Although participants perceived themselves as susceptible to cervical cancer and acknowledged its severity, there was a lack of knowledge of the link between HPV and cervical cancer, and they expressed a number of misconceptions. The most frequent barriers to screening included embarrassment, discomfort, and fear of the results. Women in both phases were receptive to self-collected sampling for HPV testing. All participants in the usability phase expressed that self-collection was easy and they did not experience any difficulties. Conclusion: Self-collection for HPV testing is an acceptable and feasible method among AA women in the Mississippi Delta to complement current cytology cervical cancer screening programs. © 2013 Jacobs Institute of Women's Health.