CONTEXT: Approximately 11% of cancer survivors smoke postdiagnosis. OBJECTIVES: Understanding the relationship between smoking and perceived cancer-related symptoms may inform tobacco treatment interventions for this population. METHODS: From 2017 to 2021, 740 adults in 9 ECOG-ACRIN trials provided baseline data. The effects of smoking status on symptoms were evaluated using logistic regression, adjusting for age, gender, race, performance status, treatment setting, and anxiety. Fisher's exact test was used to compare the prevalence of patients reporting that smoking helps/worsens each symptom by smoking status (current vs. former). RESULTS: Among participants (mean age = 58.8, 93.9% white, 30.3% female, most common cancer types: leukemia [35.5%], lymphoma [19.1%], and prostate [17.7%]), smoking statuses were: 81 current (10.9%), 257 former (34.7%), and 402 (54.3%) never. Patients currently smoking were more likely to experience cough compared to those who formerly (OR = 3.25, P <
.0001) or never (OR = 3.70, P <
.0001) smoked. Current smoking was associated with greater severity of cough and pain and greater pain interference compared to former and never smoking (OR's >
2.26, P's <
.005). Patients currently smoking were more likely to report that smoking helps with nausea (29.4% vs. 1.3%, P <
.0001), insomnia (16.4% vs. 0.6%, P <
.0001), and pain (16.1% vs. 2.8%, P = .002) compared to those who formerly smoked. CONCLUSION: Patients currently smoking report greater severity of cancer-related symptoms (i.e., cough, pain) yet were also more likely to believe that smoking helps with nausea, insomnia, and pain. Symptom management should include tobacco cessation, education on smoking and its relationship to symptoms, and strategies to reduce reliance on smoking for symptom relief.