Currently, stem cells are reported to be involved in tumor formation, drug resistance and recurrence. Inhibiting the proliferation of tumor cells, promoting their senescence and apoptosis has been the most important anti-tumor therapy. Epigenetics is involved in the regulation of gene expression and is closely related to cancer and stem cells. It mainly includes DNA methylation, histone modification, and chromatin remodeling. Histone methylation and demethylation play an important role in histone modification. Histone 3 lysine 27 trimethylation (H3K27me3) induces transcriptional inhibition and plays an important role in gene expression. Jumonji domain-containing protein-3 (JMJD3), one of the demethyases of histone H3K27me3, has been reported to be associated with the prognosis of many cancers and stem cells differentiation. Inhibition of JMJD3 can reduce proliferation and promote apoptosis in tumor cells, as well as suppress differentiation in stem cells. GSK-J4 is an inhibitor of demethylase JMJD3 and UTX, which has been shown to possess anti-cancer and inhibition of embryonic stem cells differentiation effects. In this review, we examine how JMJD3 regulates cellular fates of stem cells and cancer cells and references were identified through searches of PubMed, Medline, Web of Science.