Evidence that smokers have heightened depressive symptoms and report smoking in response to negative affect has led to an interest in mindfulness- and acceptance-based strategies to help smokers respond more adaptively to depressive symptoms. More research is needed to examine the role of emotional nonacceptance (ie, the tendency to judge or negatively evaluate one's emotions) in the relation between depression and smoking, particularly among populations with elevated smoking rates (eg, individuals with substance use disorders). This study examined the mediating role of emotional nonacceptance in the relation between depression and smoking among 125 smokers in residential substance abuse treatment. Participants (mean age = 35 ± 10; 60% male; 63% White) reported how many cigarettes they smoked in the past hour and completed self-report measures of emotion dysregulation (including nonacceptance) and depression. Major depressive disorder was assessed through clinical interview. Results supported the hypothesized relevance of emotional nonacceptance to recent smoking. Specifically, emotional nonacceptance was the only dimension of emotion dysregulation uniquely associated with recent smoking and mediated the relationship between depression and recent smoking. Results suggest that depression may interfere with emotional acceptance, increasing urges to smoke to escape negative affect. Targeting emotional nonacceptance may improve smoking cessation treatments for depressed individuals. (Am J Addict 2012;00:1–9)