Although cancer patients are generally strongly advised to quit smoking in order to improve treatment efficacy and survival, up to 68 % of patients who were smokers at the time of cancer diagnosis continue smoking. Psychological factors such as depression and anxiety are likely to be associated with smoking behavior following a cancer diagnosis, but the empirical evidence is scarce. This observational study aimed at estimating smoking cessation rates and assessing the effect of smoking cessation on psychological symptoms, as well as the predictive role of the same psychological variables on smoking cessation and smoking relapse following cancer surgery. As part of a larger prospective, epidemiological study, smokers (n = 175) with a first diagnosis of nonmetastatic cancer completed the Hospital Anxiety and Depression Scale, the Insomnia Severity Index, and the Fear of Cancer Recurrence Inventory. Quitters (n = 55) and pair-matched nonquitters (n = 55) were compared on each symptom at pre-quitting, post-quitting, and at a 4-month follow-up. Predictors of smoking cessation and smoking relapse, including psychological variables, were also investigated. Fifty-five patients (31.4 %) stopped smoking at least on one occasion during the study. Of the 55 quitters, 27 (49.1 %) experienced a relapse. At pre-quitting, quitters had significantly higher levels of anxiety (p = .03) and fear of cancer recurrence (p = .01) than nonquitters, symptoms that significantly diminished at post-quitting and 4 months later in this subgroup of patients. Having breast cancer significantly predicted smoking cessation (relative risk [RR] = 3.08), while depressive symptoms were a significant predictor of smoking relapse (RR = 1.07). This study highlights the importance of psychological symptoms in predicting tobacco cessation and relapse among individuals with cancer. Our findings suggest that breast cancer patients are more inclined to stop smoking than patients with other cancers, but future studies should attempt to delineate the effect on smoking cessation of gender and other demographics that characterize this subgroup. This study also suggests that a particular attention should be paid to the early management of depressive symptoms in order to prevent smoking relapse.