Nucleophagy is a selective autophagy, which selectively removes damaged or non-essential nuclear material from a cell by the autophagy pathway. Additionally, nucleophagy is crucial for promoting cell longevity and ensure body proper function. Increasing evidence has shown that nucleophagy may play a major role in such human diseases as degenerative disorders, tumorigenesis, malnutrition and metabolic disorders, parakeratosis and psoriasis. Studies indicated that nucleophagy can improve degenerative disorders by delaying premature cell senescence, prevent malnutrition and metabolic disorder via maintaining nuclear structure and releasing nutrients for energy production, and alleviate parakeratosis and psoriasis. But the activation of nucleophagy appears to be a double-edged sword. Some studies indicated that overexpression of lamin B1 delays cell senescence. During the process of nucleophagy, appropriate nucleophagy can drive RAS-induced cell senescence and DNA damage-induced cell senescence so as to restrain cell proliferation. Besides, appropriate nucleophagy can degrade excessive amount of DNA content in polyploid tumor cells. Hence, selective nucleophagy may effectively protect cells from tumorigenesis and maintain cell and tissue integrity. However, excessive nucleophagy can attack normal cells and lead to an unforeseen cytotoxicity. In this paper, some signal pathways of nucleophagy occurrence were explained and the role of nucleophagy in these human diseases was analyzed. Our review indicates that nucleophagy may be a potential target in human diseases.