Background: Although caregiving to patients with terminal illness is known to be a stressful burden to family members, little attention has been focused on work-related problems. We aimed to investigate employment status and work-related difficulties of family caregivers of terminal cancer patients, comparing with the general population. Methods: Using structured questionnaires, we assessed family caregivers of 481 cancer patients determined by physicians to be terminally ill, from 11 university hospitals and the National Cancer Center in Korea. Results: Among 381 family caregivers of terminal cancer patients (response rate, 87.6%), 169 (43.9%) were not working before cancer diagnosis, but currently 233 (63.7%) were not working. Compared with the general population (36.5%), the percentage of not working among the family caregivers was higher (OR=2.39; 95%CI= 1.73-3.29). A major reason for not working was to provide assistance to the patients (71.6%). 40.6% of those who continued working and 32.3% of those who not working family members reported extreme fatigue. Caregivers of old age, those who were female, those with a lower household income, and those caring for patients with a low performance status were not working at a more significant rate. Conclusion: Family caregivers of terminal cancer patients suffer job loss and severe work-related difficulties, probably due to caregiving itself and to fatigue. We need to develop supportive programs to overcome the burden of caregivers of the terminally ill.