The present study examined the role of individualism-collectivism (IC) and acculturation in smoking prevention programs for Hispanic preadolescents. The sixth graders received a collectivist or individualist curriculum. Both programs contained knowledge-based facts about smoking. The collectivist condition included an interdependent (group-oriented) perspective of smoking, while the individualist condition had an independent (individual-oriented) perspective. Measurements assessing attitudes and behaviors were taken before and after the implementation. Compared to the individualist program, Hispanic youth in the collectivist condition reported greater awareness about the dangers of smoking, revealed more accurate and healthier perceptions, and expressed restraint in engaging in unhealthy behaviors. Acculturation effects depended on participants’ IC characteristic. This research showed the utility of cultural dimensions in health programs for Hispanic youth. It also blends basic and applied research in furthering the prevention of smoking among minority youth.