Smoking is the largest avoidable cause of preventable morbidity worldwide. It causes most of the cases of lung cancer and chronic obstructive pulmonary disease (COPD) and contributes to the development of other lung diseases. The control of smoking is considered as a highly important intervention for the prevention of lung diseases. Tobacco consumption is highly influenced by socioeconomic factors. SmokeFreeBrain aims to address the effectiveness of a multi-level variety of interventions aiming at smoking cessation in high risk target groups within High Middle Income Countries (HMIC) such as unemployed young adults, COPD and asthma patients, as well as within the general population in Low Middle Income Countries (LMIC). The project addresses existing approaches aiming to prevent lung diseases caused by tobacco while at the same time it develops new treatments and analyzes their contextual adaptability to the local and global health care system. SmokeFreeBrain follows an interdisciplinary approach exploiting consortium’s expertise in various relevant fields in order to generate new knowledge. State of the art techniques in toxicology, pulmonary medicine, neuroscience and behavior will be utilized to evaluate the effectiveness of: (i) Public Service Announcement (PSA) against smoking, (ii) the use of electronic cigarettes with and without nicotine as a harm reduction approach and/or cessation aid, (iii) a specifically developed neurofeedback intervention protocol against smoking addiction, (iv) a specifically developed intervention protocol based on behavioral therapy, social media/mobile apps and short text messages (sms) and (v) pharmacologic interventions. The main objective of the project is to evaluate the interventions in terms of health economics, by studying their cost-effectiveness, and proposing a scalable plan and a clear pathway to embedding the proposed interventions into policy and practice both in LMIC as well as in HMIC.