The physical and psychological benefits of exercise for cancer survivors are well documented. Researchers have examined self-efficacy (SE) as a target for promoting exercise; however, the predictors of SE, including treatment factors and comorbidities, have not been examined extensively. The purpose of this cross-sectional analysis was to examine how variables related to cancer and cancer treatment, comorbid health problems, health-related quality of life (QOL), and depression relate to SE for physical activity in cancer survivors. This secondary analysis examined treatment factors, comorbidity, and QOL data from 148 breast cancer and 134 prostate cancer survivors who had participated in studies examining exercise and QOL. A predictive regression model was developed by testing each variable individually with SE and including the variables that had a significance of <or=0.2 in a multivariate regression model. For the breast cancer population, vitality (B=0.23, p=0.02), bodily pain (B=0.16, p=0.07), and mental health (B=0.15, p=0.01) were associated with SE for physical activity. For the prostate cancer survivors, education, (B=-0.20, p=0.036) vitality (B=0.26, p=0.01), and bodily pain (B=0.13, p=0.182) remained in the model. Treatment factors and comorbidities were not associated with SE for physical activity, but health-related QOL factors of vitality and bodily pain were associated with SE. Thus, subjective measures of well-being are important factors to consider when developing targeted interventions to increase physical activity in cancer survivors.