ABSTRACT: BACKGROUND:Smoking rates in the United States have been reduced in the past decades to 15% of the general population. However, up to 88% of people with psychiatric symptoms still smoke, leading to high rates of disease and mortality. Therefore, there is a great need to develop smoking cessation interventions that have adequate levels of usability and can reach this population. OBJECTIVE:The objective of this study was to report the rationale, ideation, design, user research, and final specifications of a novel smoking cessation app for people with serious mental illness (SMI) that will be tested in a feasibility trial. METHODS:We used a variety of user-centered design methods and materials to develop the tailored smoking cessation app. This included expert panel guidance, a set of design principles and theory-based smoking cessation content, development of personas and paper prototyping, usability testing of the app prototype, establishment of app's core vision and design specification, and collaboration with a software development company. RESULTS:We developed Learn to Quit, a smoking cessation app designed and tailored to individuals with SMI that incorporates the following: (1) evidence-based smoking cessation content from Acceptance and Commitment Therapy and US Clinical Practice Guidelines for smoking cessation aimed at providing skills for quitting while addressing mental health symptoms, (2) a set of behavioral principles to increase retention and comprehension of smoking cessation content, (3) a gamification component to encourage and sustain app engagement during a 14-day period, (4) an app structure and layout designed to minimize usability errors in people with SMI, and (5) a set of stories and visuals that communicate smoking cessation concepts and skills in simple terms. CONCLUSIONS:Despite its increasing importance, the design and development of mHealth technology is typically underreported, hampering scientific innovation. This report describes the systematic development of the first smoking cessation app tailored to people with SMI, a population with very high rates of nicotine addiction, and offers new design strategies to engage this population. mHealth developers in smoking cessation and related fields could benefit from a design strategy that capitalizes on the role visual engagement, storytelling, and the systematic application of behavior analytic principles to deliver evidence-based content.