BackgroundTobacco use is the leading cause of preventable morbidity and mortality. Adults with low income and members of certain racial and ethnic minority groups are less likely to quit, and therefore, they experience profound tobacco-related health disparities. Mindfulness training can increase the rates of smoking cessation and lapse recovery, and telehealth and SMS text messaging have the potential to provide more accessible treatment.ObjectiveThis study aims to test the efficacy of delivering mindfulness-based smoking cessation treatment through text messaging (iQuit Mindfully) and telehealth (group videoconferencing), both as stand-alone interventions and in combination. In addition, it aims to examine the underlying mechanisms of mindfulness treatment.MethodsIn this 2×2 randomized controlled trial, participants are randomized into 1 of 4 groups based on assignment to iQuit Mindfully text messages (yes or no) and mindfulness videoconference groups (yes or no). The primary outcomes are biochemically verified smoking abstinence at 8, 12, and 24 weeks after the start of treatment. Secondary outcomes include the frequency of home mindfulness practice and self-reported levels of mindfulness, emotions, craving, withdrawal, dependence, self-efficacy, and social support.ResultsRecruitment, treatment, and assessment began in spring and summer 2021, and data collection is expected to continue through spring 2024.ConclusionsThis project aims to improve smoking cessation outcomes for low-income, racially and ethnically diverse smokers through mindfulness-based telehealth group counseling and text messaging support. We also aim to advance the scientific study of the mechanisms of action of mindfulness treatment, which could inform the development of more efficacious and efficient treatments to reduce tobacco disparities.Trial RegistrationClinicaltrials.gov NCT04965181; https://clinicaltrials.gov/ct2/show/NCT04965181International Registered Report Identifier (IRRID)PRR1-10.2196/35688