Endometrial cancer (EC) is an epithelial malignant tumor in women. Copine-1 (CPNE1) is an oncogene implicated in many tumors. Nevertheless, the influence of CPNE1 on EC has not been fully determined. This study aims to determine the impact of CPNE1 on EC. In this research, User-friendly Analysis of Cancer Gene Expression Data (UALCAN) was used to analyze CPNE1 expression in uterine corpus endometrial carcinoma (UCEC) and its effect on patient survival probability. The levels of CPNE1, hexokinase 2 (HK2), phosphorylated Akt kinas/Akt kinas (p-AKT/AKT), and c-myc were examined by western blot or quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8) assay and clone formation assay. The glucose consumption, lactate production, and adenosine triphosphate (ATP) levels in Ishikawa and KLE cells were measured by commercial kits. We found that the expression of CPNE1 was upregulated in EC and closely related to the development of EC. Silencing CPNE1 suppressed proliferation and aerobic glycolysis of EC cells. Silencing CPNE1 inhibited AKT/c-myc pathway in EC cells. Downregulation of CPNE1 also inhibited proliferation and aerobic glycolysis of EC cells via regulating the AKT pathway. In conclusion, CPNE1 plays an oncogenic role in EC and silencing CPNE1 reduces proliferation and aerobic glycolysis of EC cells through modulation of the AKT pathway.