Objective: Despite efforts to reduce cancer disparities, Black women remain underrepresented in cancer research. Virtual health assistants (VHAs) are one promising digital technology for communicating health messages and promoting health behaviors to diverse populations. This study describes participant responses to a VHA-delivered intervention promoting colorectal cancer (CRC) screening with a home-stool test. Methods: We recruited 53 non-Hispanic Black women 50 to 73 years old to participate in focus groups and think-aloud interviews and test a web-based intervention delivered by a race-and gender-concordant VHA. A user-centered design approach prioritized modifications to three successive versions of the intervention based on participants' comments. Results: Participants identified 26 cues relating to components of the VHA's credibility, including trustworthiness, expertise, and authority. Comments on early versions revealed preferences for communicating with a human doctor and negative critiques of the VHA's appearance and movements. Modifications to specific cues improved the user experience, and participants expressed increased willingness to engage with later versions of the VHA and the screening messages it delivered. Informed by the Modality, Agency, Interactivity, Navigability Model, we present a framework for developing credible VHA-delivered cancer screening messages. Conclusions: VHAs provide a systematic way to deliver health information. A culturally sensitive intervention designed for credibility promoted user interest in engaging with guideline-concordant CRC screening messages. We present strategies for effectively using cues to engage audiences with health messages, which can be applied to future research in varying contexts. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.