This study examined the communication effects of smoking cessation by using message framing (positive messages/negative messages) and audience situation (smoker/nonsmoker and high/low self-efficacy). The study used 207 valid homogeneous subjects and a between-subject experiment method was employed for analyses. The results showed that the communication effects were influenced by the interactive effects of message framing and audience situation, and for smokers, positive messages have a more significant effect than negative ones. In addition, positive messages with low self-efficacy have a better effect. The study concludes that different message framing have a variety of communication effects on audiences within different self-efficacy levels and audience situations.