This study examined whether (a) cancer patients in two cohorts reported greater subjective cognitive impairment (SCI) in prevalence and severity than noncancer healthy controls; and (b) selected psychoneurological factors (fatigue, stress, and sleep disturbance) contribute to such differences. Data from 60 prechemotherapy cancer patients, 81 active-chemotherapy cancer patients, and 116 noncancer healthy controls were analyzed using hierarchical regressions. The prevalence rate of SCI was higher in the prechemotherapy cancer cohort (41.6%) and in the active-chemotherapy cancer cohort (46.9%) than in healthy controls (21.5%;  < .001). SCI severity was also higher in two cancer cohorts than noncancer controls ( < .001). The two cancer cohorts were similar to each other in severity and prevalence of SCI. The two cancer cohorts experienced higher fatigue, stress, and sleep disturbance than healthy controls. After controlling for psychoneurological factors, however, the two cancer cohorts did not differ from healthy controls in experiencing SCI in prevalence and severity. Psychoneurological factors may be a major determinant of the higher prevalence and severity of SCI in cancer patients.