Introduction Tobacco use is a major contributor to the burden of chronic obstructive pulmonary disease (COPD) and other non-communicable diseases in China. People at high risk for COPD who smoke, particularly those with pre-existing chronic conditions, often remain underserved by conventional smoking cessation programmes. Population medicine offers a promising framework for proactively identifying high-burden diseases, managing multimorbidity and prioritising interventions for vulnerable populations. Methods and analysis This protocol describes a stratified, two-arm cluster randomised controlled trial (Population Medicine Multimorbidity Intervention in Xishui County-Smoking) being conducted in Xishui County, a rural area of Guizhou Province, China. A total of 26 townships were stratified by population size and randomly assigned in a 1:1 ratio to receive either a multicomponent intervention or usual care. Eligible participants were individuals aged 35 years or older who smoked and were at high risk for COPD as identified by the COPD Screening Questionnaire. The intervention package integrates multiple components, including a digital smoking cessation programme, digital mental health support, community-based spirometry, tailored chronic disease management, health education and a performance-linked ‘pay-for-population’ scheme that aligns healthcare worker reimbursement with population health outcomes. Primary outcomes are smoking amount and nicotine dependence and secondary outcomes include COPD-related health outcomes, hypertension, diabetes, health risk behaviours, quality of life, healthcare utilisation and productivity loss. Follow-up occurs at 3, 6 and 12 months. Ethics and dissemination Ethical approval has been granted by the Peking Union Medical College Ethics Committee (CAMS&PUMC-IEC-2024-042). Informed consent was obtained from all participants prior to enrolment. Results will be shared through peer-reviewed publication and (inter)national conference presentations. Trial registration number NCT06458205 .
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