Spermatogenesis originates spermatogonial stem cells (SSCs). SSCs can continually renew and eventually differentiate into spermatozoa under control of various growth factors, microenvironments and self-signaling. The molecules involved in SSCs self-renewal include glial cell-derived nerve growth factor, fibroblast growth factor and downstream signaling pathways, as well as the transcription factors and the epigenetic regulators. Molecules related to SSCs differentiation include retinoic acid, a variety of transcription factors and the eptigenetic regulatory factors. The research on the mechanism of SSCs self-renewal and differentiation is of great significance for the understanding of spermatogenesis and the diagnosis and treatment of male infertility. This review summarized the exogenous factors, transcription factors, and epigenetic regulators that are involved in the regulation of SSCs self-renewal and differentiation in recent years.