Recent studies indicate that serum response factor (SRF) is highly expressed in tumors such as hepatocellular, thyroid, esophageal and lung carcinoma. However, the expression and roles of SRF in esophageal squamous cell carcinoma (ESCC) are unclear. In this study, immunohistochemistry was used to compare the expression of SRF in ESCC cases (n=73) and normal controls (n=30). The RNA interference (RNAi) technique was used to knock down the expression of SRF in Eca-109 cells. Cell proliferation, cell cycle stage and invasion were measured with cell counting kit (CCK)-8, flow cytometry and Transwell assays, respectively. Western blotting was used to measure SRF, E-cadherin, beta-catenin and cyclin D1 expression in Eca-109 cells treated with siRNA. The study demonstrated that human ESCC has increased expression of SRF. In addition, blocking SRF expression inhibited tumor proliferation and invasion. In conclusion, SRF has the potential to be a new marker for ESCC diagnosis and therapy.