Effective prevention of tobacco use among children and adolescents is critical to achieving elimination of tobacco-attributable cancers. The National Institute of Public Health of Mexico and Instituto de Cancerologia Las Americas, two Sister Institution Network partners, enthusiastically signed agreements to culturally adapt and pilot-test MD Anderson’s online, interactive multimedia program for their countries. “ASPIRE is a tested tobacco prevention and cessation curriculum designed for culturally diverse high school students in the United States. It was proven to be effective for reducing tobacco uptake. The intervention covers both the prevention and cessation of conventional and new and emerging tobacco products. Participants (n = 50) aged 11 to 18 years from Latin American middle and high schools will work through ASPIRE online. Research activities will include culturally adapting and testing ASPIRE for Latin American adolescents. Its core elements and behavioral theory underpinnings will remain intact after cultural adaption.