Low dose computed tomography (LDCT) is an effective screening test to decrease lung cancer deaths. Lung cancer screening may be a teachable moment helping people who smoke to quit, which may result in increased benefit of screening. Innovative strategies are needed to engage high-risk individuals in learning about LDCT screening. More precise methods such as polygenic risk scores quantify genetic predisposition to tobacco use, and optimize lung health interventions. We present the ESCAPE (Enhanced Smoking Cessation Approach to Promote Empowerment) protocol. This study will test a smoking cessation intervention using personal stories and a lung cancer screening decision-aide compared to standard care (brief advice, referral to a quit line, and a lung cancer screening decision-aide), examine the relationship between a polygenic risk score and smoking abstinence, and describe perceptions about integration of genomic information into smoking cessation treatment. A randomized controlled trial followed by a sequential explanatory mixed methods approach will compare the efficacy of the interventions. Interviews will add insight into the use of genomic information and risk perceptions to tailor smoking cessation treatment. Two-hundred and fifty individuals will be recruited from primary care, community-based organizations, mailing lists and through social media. Data will be collected at baseline, 1, 3 and 6-months. The primary outcomes are 7-day point prevalence smoking abstinence and stage of lung cancer screening at 6-months. The results from this study will provide information to refine the ESCAPE intervention and facilitate integration of precision health into future lung health interventions.Clinical trial registration number: NCT0469129T.