Background <p>Prior studies emphasize the impact of anti-tobacco campaigns on tobacco prevention; there needs to be more understanding of the variations across different media channels. This study examines the associations between cigarette use, harm perception of e-cigarettes, and e-cigarette use, and explores how exposure to offline and online anti-tobacco messages is related to these associations.</p> Methods <p>Utilizing data from the HINTS 6 (<i>N</i> = 5,268), this study employs mediation analysis to explore two primary mediating mechanisms: [1] the mediating role of offline and online anti-tobacco message exposure and [2] the sequential mediating effect involving offline and online anti-tobacco messages and harm perception of e-cigarettes.</p> Results <p>Our findings revealed that cigarette use was positively associated with e-cigarette use (B=0.260, <i>β</i> = 0.256, <i>p</i>&lt;.001). While offline anti-tobacco messages exposure showed no significant mediating effect (B=0.002, <i>β</i> = 0.002, [-0.001, 0.005]) between cigarette use and e-cigarette use, and it became a substantial and negative mediator when introducing harm perception of e-cigarettes (B=-0.001, <i>β</i>=-0.001, [-0.002, − 0.001]). Conversely, online anti-tobacco messages exposure positively mediated the link between cigarette use and e-cigarette use (B=0.004, <i>β</i> = 0.004, [0.001, 0.007]), but was not significantly associated with harm perception of e-cigarettes (B=-0.022, <i>β</i>=-0.007, <i>p</i>&gt;.05).</p> Conclusions <p>This study reaffirms the prevalence of dual use and reveals the disparities between online and offline anti-tobacco messages exposure. The distinctive roles played by online and offline media channels and the pivotal influence of harm perception of e-cigarettes on e-cigarette use carry significant implications for public health and tobacco control.</p>