PROJECT SUMMARY/ABSTRACT Markey Cancer Center’s (MCC) Cancer Prevention and Control (CP) Research Program fosters high-impact, population-based and community-engaged research with the overarching goal of reducing cancer incidence and mortality in Kentucky. CP research spans the population science translation pipeline from advancing understanding of risk factors and intervention targets, to developing and testing new interventions, to studying the process of dissemination and implementation of interventions into practice. Impactful scientific contributions include research into patient survival in oropharyngeal cancer, timely regulatory and policy research on novel smokeless tobacco products, trials of innovative interventions to reduce carcinogenic environmental exposures, trials of interventions to promote quality of life outcomes among rural cancer survivors, and community implementation trials to prevent hepatitis C transmission and implement cancer prevention and screening guidelines in communities throughout Kentucky and Appalachia. CP impact also extends to public health policy within Kentucky and nationally, and in advancing standards of care related to tobacco cessation and lung cancer screening. The CP Program combines these strengths to address three Aims: Advance the understanding of risk factors and intervention targets for cancer prevention and control (Aim 1); Develop and test the efficacy of interventions across the cancer control continuum (Aim 2); Study the dissemination and implementation of interventions (Aim 3). The CP Program has been transformed by substantial strategic investments that have led to new leadership and by the infusion of multiple recruitments that have expanded the breadth and depth of program research, combined with the continued success of long-standing program members. The program’s peer-reviewed funding has increased by 50%, and NCI funding has grown dramatically by 567% to now comprise 33% of peer-reviewed funding, compared to 7% in 2017. The maturation of the program is evident in a 24% increase in clinical trial accrual and by the awarding of NCI P01 and UH3 multi-investigator, inter-institutional grants and an NCI T32 focused on rural cancer. CP investigators are highly engaged with and responsive to the needs of MCC’s catchment area residents and are engaged in inter-programmatic research that addresses MCC’s catchment research priorities, in collaboration with Community Outreach and Engagement. Thus, the CP Program is integral to achieving the overall MCC mission to reduce cancer in Kentucky through research, prevention, treatment, education and community engagement.