Research has suggested that shiftwork is associated with negative physical and psychological symptoms. Such results are consistent with the biopsychosocial model of stress, which formed the theoretical foundation for the current study. However, research on the association between shiftwork and negative psychological symptoms is sparse and has typically relied on measures that do not reflect DSM-IV-TR diagnostic criteria. Studies using measures linked to DSM-IV-TR diagnostic criteria have either relied on limited participant samples or yielded nonsignificant results. Consequently, there is still a lack of data on the psychological impact of shiftwork on hospital nurses. The purpose of this study was to explore the relationship between shiftwork and symptoms of anxiety and depression among hospital nurses. A sample of 133 female hospital nurses who were engaged in shiftwork completed an online survey, which consisted of the Standard Shiftwork Index, Center for Epidemiologic Studies Depression Scale, and Generalized Anxiety Disorder Seven-Item Scale. Multiple regression analyses showed that shiftwork was not significantly related to anxious and depressive symptoms. However, hours of sleep significantly moderated the relationship between shiftwork and depressive symptoms and use of disengagement coping strategies significantly moderated the relationship between shiftwork and anxious symptoms. The results of this study help (a) clarify the relationship between shiftwork and symptoms of anxiety and depression and (b) identify factors that moderate those symptoms among hospital nurses who engage in shiftwork. The results of this study contribute to social change by identifying factors that enhance the overall health of hospital nurses, thereby increasing patient safety.