Background: Endometrial cancer (EC) is one of the most common gynecologic cancers of the female reproductive system. Its incidence and mortality are currently increasing. Patients with early-stage EC have a much better prognosis than those with late-stage EC. Therefore, early detection, diagnosis, and treatment are critical to improving the outcome for EC patients. The proposition of molecular classification promotes the individualization for diagnosis and treatment of EC. TCOF1 has been identified as an oncogenic gene in several tumors but has been seldom studied in EC. Methods: TCGA and immunohistochemistry (IHC) experiments were performed to verify the protein level of TCOF1 expressed in endometrial cancer while its prognostic ability in EC patients was assessed by the TCGA database. Linked Omics database, Web Gestalt gene enrichment, and string database were applied to analyze the possible biological functions of TCOF1 in EC. Mutation types of TCOF1 in EC and its mutation frequency were explored in c-BIOPORTAL. The Relationship between molecules was detected by utilizing the GEPIA database. Results: TCOF1 is up-regulated in endometrial cancer compared to para cancer and it was positively correlated with poor prognosis of patients. TCOF1 is mutated in endometrial cancer and is closely associated with microsatellite instability (MSI), this being one type of molecular classification in EC. Conclusions: TCOF1 may function as a potential biomarker and is associated with molecular classification in endometrial cancer.