The internet is becoming a common platform for individuals to seek and assess information. How heuristic cues in an online environment such as website background color influence information persuasiveness, however, is somewhat underexplored. This study examines the effect of such cues based on the MAIN model and color/gender-related stereotypes. A 2 (health message topic: breast cancer vs. prostate cancer) × 2 (website background color: pink vs. blue) × 2 (audience gender: female vs. male) between-subjects experiment (N = 224) was conducted, and the results revealed significant three-way interaction effects that men and women’s perceptions of message credibility, informativeness, as well as their attitudes toward cancer screening were affected by message topic and background color.