Psychological distress is elevated among smokers and plays a key role in the maintenance of smoking behavior. Although research has implicated emotion regulation (ER) difficulties as a transdiagnostic construct for psychological distress, empirical work has not yet investigated ER difficulties among treatment-seeking smokers. The purpose of the current study was to increase understanding of ER difficulties in relation to depression, anxious arousal, and functional impairment among treatment-seeking smokers. Participants included adult daily treatment-seeking smokers (N = 568; Mage = 37, SD = 13.46; 51.9% male). Results indicated that global ER difficulties were significantly related to depression, anxious arousal, and functional impairment. Analyses focused on the lower-order facets of ER and indicated that limited access to ER strategies, difficulty engaging in goal-directed behavior, and lack of emotional clarity were significantly related to depression; limited access to ER strategies, nonacceptance of emotions, and impulsivity were significantly associated with anxious arousal; and limited access to ER strategies and difficulty engaging in goal-directed behavior were significantly related to functional impairment. The significant ER effects were evident above and beyond the variance accounted for by neuroticism and tobacco dependence. These findings highlight the importance of considering ER difficulties to better understand psychological distress among smokers.