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Serum response factor (SRF) is a transcription factor that regulates many genes involved in cellular activities such as proliferation, migration, differentiation, angiogenesis, and apoptosis. Although it has only been known for about two decades, SRF has been studied extensively. To date, over a thousand SRF studies have been published, but it still remains a hot topic. Due to its critical role in mesoderm-derived tissues, most of the SRF studies focused on muscle structure/function, cardiovascular development/maintenance, and smooth muscle generation/repair. Recently, SRF has received more attention in the digestive field and several important discoveries have been made. This review will summarize what we have leed about SRF in the gastrointestinal tract and provide insights into possible future directions in this area.