Purpose: Homeless adults have a higher prevalence of smoking compared to the general population. Most tobacco cessation efforts have focused on the general population, with limited attention paid to this vulnerable population. In this study, homeless adults as well as shelter staff were interviewed to understand their attitudes and beliefs about smoking and smoking cessation, and receptiveness to smoking cessation interventions. Methods: Semi-structured, one-on-one interviews were audio recorded and transcribed for 13 homeless adult smokers and 9 staff recruited from a homeless shelter in Charleston, South Carolina. Transcripts were analyzed in a systematic manner by independent investigators trained in grounded theory. The constant comparison method was used to code, categorize and synthesize the qualitative data. Results: The majority of smokers interviewed expressed the desire to stop smoking, but felt that stress from being homeless was a barrier to quitting. When asked about different tobacco cessation methods, there was no preferred method and there was skepticism regarding actual effectiveness of different methods, since many had previously been unsuccessful when tried by these smokers. Shelter staff acknowledged that tobacco cessation was important, but did not see it as a priority for shelter residents. Even though cessation medications are available in the shelter clinic, very few of the smokers or shelter staff interviewed were aware of the availability of these medications. Conclusions: This study suggests that adult smokers in a homeless shelter are interested in quitting smoking and receptive toward assistance, but that lack of awareness and perceived importance of cessation among staff is a significant barrier. Providing training to staff and encouraging them to take a proactive approach to tobacco cessation may be an area to focus future cessation interventions.