c-fos is an immediate early gene (IEG) that forms a heterodimeric activator protein-1 (AP-1) complex with c-Jun. Following stimulation by a variety of factors, it changes the expression of genes and participates in cellular growth, proliferation, differentiation, and apoptosis. Previous studies have reported that c-fos is linked to cellular senescence and is involved in aging-related signaling pathways or damage repair processes. However, there are limited studies related to this topic. This review summarizes the findings of the connection between c-fos and cellular senescence, including the regulatory role of c-fos in the senescence of stem cells and various kinds of somatic cells. In addition, we discussed the involvement of c-fos in the cellular senescence process and related signaling pathways, as well as the importance of regulating DNA damage repair. The current studies have demonstrated that c-fos has important roles in inhibiting stem cell senescence. They can pave the way for a more thorough examination of the aging process and the regeneration of stem cells and provide new therapeutic strategies for aging-related diseases.