Background: A high proportion of smokers suffer from mental health problems including depression. Despite many of them wanting to stop smoking, low mood adversely affects their ability to quit. Objective: To explore the experiences of smokers with self-reported depression, the relationship of smoking with mental health problems and the experiences of smokers while trying to quit. The study also explored what help within the primary care setting could assist in quitting. Methods: Participants were recruited from a large general-practice-based smoking cessation trial. Participants who had indicated they were suffering from depression on a self-reported baseline survey were invited to participate. Semi-structured interviews were conducted over the telephone and digitally recorded. The interviews were transcribed and analysed using a phenomenological qualitative approach. Results: Sixteen interviews were conducted (11 females, 5 males). Mood disturbances were frequently reported as triggers for smoking and low mood was seen as a barrier to quitting. Perceived benefits of smoking when depressed were limited and for many, it was a learned response. A sense of hopelessness, lack of control over one's life and a lack of meaningful activities all emerged as important factors contributing to continued smoking. Participants felt that their quit attempts would be aided by better mood management, increased self-confidence and motivation and additional professional support. Conclusions: Smoking and depression were found to be strongly interconnected. Depressed smokers interested in quitting may benefit from increased psychological help to enhance self-confidence, motivation and mood management, as well as a supportive general practice environment.