The number of empty-nest elderly is on the rise, especially in rural areas of China. The empty-nest elderly were concerned from social and demographic perspective, but researches on mental health issues of the aged were still rare in China. To clarify the prevalence of depression among empty-nest elderly in a rural area of YongZhou, Hunan and evaluate the impact of social support, coping style and socio-demographic factors on depression of the empty-nest elderly, with the goal of decreasing the rate of depression in empty-nest elderly, a questionnaire survey was conducted on 415 elderly persons. The determined prevalence of depressive symptoms was 74.46%. The empty-nest group, in comparison with the non-empty nest group, had higher levels of depression. Multivariate linear regression analysis showed associations between depressive symptoms and negative coping style, support utilization, religious beliefs, economic status, marital status and subjective support. The results suggested that the strategy to alleviate the depression in empty-nest elderly can be considered by the society, village committee, the family members and the empty-nest elderly subjects themselves, which could control effectively the incidence of depression.