Introduction: Forkhead box M1 (FOXM1) is considered as a novel anti-cancer target, because it has many essential functions such as mitosis regulation, cell cycle transition, and other carcinogenesis signaling pathways. Dachshund homolog 1 (DACH1) is a member of the Sno/Ski co-repressor family. Material and methods: Expression of DACH1 has been detected in many cancers. Patients and pathologic specimens: 50 patients with endometrial cancer (EC) were included in the study: ten specimens of normal endometrium and twenty specimens of endometrial hyperplasia. All samples underwent processing to investigate FOXM1 and DACH1 expression using immunohistochemistry. Results: FOXM1 expression was detected in EC tissues more than normal endometrium and endometrial hyperplasia tissues (p = 0.001) and 0.01. Increased FOXM1 expression was positively associated with larger tumor size (p = 0.002), high grade (p = 0.004), myometrial invasion, presence of lymph node metastases, higher Federation of Gynecology and Obstetrics (FIGO) stage (p < 0.001), and worse progression-free survival (PFS) and overall survival (OS) rates. The expression of DACH1 was lower in EC cells than normal endometrium and endometrial hyperplasia tissues (p = 0.071) and 0.252. Low DACH1 expression was associated with high grade (p = 0.001), presence of lymph node metastases (p = 0.49), higher FIGO stage (p = 0.022), and unfavorable PFS and OS rates (p = 0.037). We found an inverse association between expression of FOXM1 and DACH1 in EC tissues and in non-neoplastic endometrial tissues (p = 0.007). Conclusions: FOXM1 over-expression and DACH1 down-regulation in EC were related to poor clinical and pathological parameters and unfavorable prognosis.