Cigarette smoking, which is presently associated with more than 20% of adult deaths in the United States, is a large confounder to radiation risk estimates derived from epidemiology data. Astronauts and other exposed groups are classified as never-smokers (NS), defined as lifetime use of less than 100 cigarettes. In the past, radiation risk estimates have been made using average U.S. population rates for cancer and all causes of death, which may lead to overestimation of radiation risks for NS. In this report, age- and gender-specific radiation carcinogenesis risk calculations for NS and the average U.S. population are compared. Lung is the major tissue site for smoking and radiation-related cancer. However, other radiogenic cancers where tobacco has been shown to increase population cancer rates are esophagus, oral cavity, salivary gland, bladder, stomach, liver, colorectal, and leukemia. After adjusting U.S. cancer rates to remove smoking effects, radiation risks for lung and other cancers were estimated using the multiplicative risk model and a mixture model, with weighted contributions for additive and multiplicative risk transfer. Radiation mortality risks for NS were reduced compared to the average U.S. population by more than 20% and 50% in the mixture model and multiplicative transfer models, respectively. The authors discuss possible mechanisms of cancer risks from radiation and tobacco that suggest multiplicative effects could occur. These results suggest that improved understanding of possible synergisms between cancer initiators and promoters, such as radiation and tobacco, would greatly improve risk estimates and reduce uncertainties for differentially exposed groups, including NS.