Tobacco use poses a significant health risk to the Thai population, contributing to serious illnesses such as cancer and lung disease while also increasing the risk of tuberculosis. This six-month quasi-experimental study, conducted in Phrae Province, Thailand, aims to assess the effectiveness of the mobile phone mini-game, “Duet Me,” with its engaging design and HBM alignment in enhancing tobacco knowledge among adolescents. A sample of 99 fifteen-year-olds participated, with the focus on a two-month intervention period and a four-month follow-up. Data were collected through self-administered questionnaires. Demographic analysis revealed that the intervention group comprised 51% females, and the comparison group comprised 54% females. Approximately 23.2% of participants reported prior tobacco use. Both groups initiated the study with a low level of knowledge (p-value>0.05). The intervention group exhibited a significant increase in tobacco knowledge at both the two-month post-intervention and four-month follow-up, outperforming the comparison group (p-value<0.05). Repeated measures ANOVA revealed a significant difference in the mean knowledge scores between the two groups over time, supporting the game’s effectiveness (p-value<0.0001). Pairwise comparison confirmed sustainable knowledge improvement in the intervention group (p-value<0.0001). The findings suggest that innovative interventions play a positive role in promoting health education among adolescents, potentially contributing to fostering informed decision-making toward tobacco consumption.