Abstract: In this research, we seek to provide effective message strategies to communicate stigma associated health issues such as the human papillomavirus (HPV), by exploring the roles of humor, STD information, and objective HPV knowledge. Conducted with a 2 (Humor: no vs. yes) x 2 (STD information: no vs. yes) between-subjects experiment with objective HPV knowledge as a measured moderator, findings suggested that for the lower HPV knowledge subjects, the humor ads produced higher attention to the ad, more favorable ad attitudes (Aad), and greater behavioral intention to seek HPV prevention and treatment than the no-humor ads when there is no STD information. However, when STD information was present, for the lower HPV knowledge individuals, the no-humor ads produced greater attention and more positive Aad than the humor ads. Humor and STD information in the ads did not affect higher HPV knowledge individuals. Implications for theory as well as practice are discussed.