Objectives/Goals: People experiencing homelessness (PEH) face excess cervical cancer burden and unique barriers to screening. As part of a broader study addressing cervical cancer disparities in homeless populations in Indiana, our goal was to engage unhoused women in a human-centered design process to inform a homeless shelter-based self-sampling intervention. Methods/Study Population: An established community-academic partnership enabled meaningful engagement of homeless communities in Indiana and informed the need to understand and address cervical cancer disparities in this population. Rapid assessment surveys (n = 202) and in-depth interviews (n = 30) were conducted with PEH at two major shelters in Indianapolis and Lafayette to understand cervical cancer screening coverage, knowledge, attitudes, and practices; barriers and facilitators; and acceptability of human papillomavirus (HPV) self-sampling for onsite shelter-based screening. A human-centered design session with (n = 12) unhoused women further explored motivators and concerns regarding self-sampling and informed key messages and informational materials to encourage uptake of screening. Results/Anticipated Results: At least 37% were overdue for screening (last screened >5 years ago; 50% were last screened >3 years ago), far greater than national (22%) or state (24%) averages. Despite common misconceptions regarding indifference toward preventive healthcare among homeless populations, most (87%) wanted to be screened and believed it is important for their health. Competing priorities for daily survival, transportation, cost, provider mistrust, stigma, and related trauma were common barriers to screening. Enthusiasm for HPV self-sampling centered on convenience, privacy, and comfort in taking one’s own sample at the shelter. Notable concerns included lack of confidence regarding ability to self-sample correctly, unhygienic conditions in shelter restrooms, preference to be seen by a doctor, and the need for education. Discussion/Significance of Impact: The unique challenges of PEH require human-centered strategies to improve cervical cancer screening access. Willingness to be screened and acceptability of HPV self-sampling is high. Identified concerns and preferences will guide implementation of HPV self-sampling delivered by trusted community health workers in homeless shelters in Indiana.