Background: Endometrial cancer (EC) is a prevalent malignancy of the female reproductive system. To investigate the function of Ubiquitin-associated protein 2 (UBAP2L) has been linked to various cellular processes and cancer progression. However., its role in EC is still unclear. Methods: UBAP2L expression was analyzed in endometrial cancer tissues using data from the TCGA and Kaplan-Meier databases. siRNA was employed to knock down UBAP2L in EC cell lines. Cell growth and motility were assessed via CCK8 assays, wound healing, as well as Transwell, respectively. Immunoblot was used to explore the involvement of the phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) axis. Results: UBAP2L expression was significantly upregulated in EC tissues. Knockdown of UBAP2L in human endometrial cancer-1A (HEC-1A) as well as Ishikawa cells suppressed cell growth, stimulated cell cycle arrest, and suppressed motility. Mechanistically, UBAP2L silencing suppressed the PI3K/AKT pathway. Conclusions: UBAP2L plays a critical role in promoting the growth and migration of endometrial cancer cells via the PI3K/AKT axis.