Endometrial cancer (ECa) is a common gynecological malignancy. Circular RNAs (circRNAs) have been identified as key regulators of human tumorigenesis and development. Herein, we explored the role and mechanism of circular RNA intraflagellar transport 80 (circ-IFT80, also called circ_0067835) in ECa.Circ-IFT80, microRNA-545-3p (miR-545-3p), and family with sequence similarity 98 member A (FAM98A) were quantified by quantitative real-time polymerase chain reaction or Western blot. The biological characteristics of ECa cells were evaluated via Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, transwell, tube formation and flow cytometry assays. Dual-luciferase reporter assay or RNA pull-down assay was employed to verify the binding relationship between miR-545-3p and circ-IFT80 or FAM98A. Xenograft assays were conducted to analyze the effect of circ-IFT80 in vivo.Circ-IFT80 and FAM98A were up-regulated, and miR-545-3p was down-regulated in ECa tissues and cells. Knockdown of circ-IFT80 blocked proliferation, migration, invasion and angiogenesis and promoted apoptosis in ECa cells. Moreover, circ-IFT80 harbored a binding site for miR-545-3p, and the effects of circ-IFT80 were mediated by miR-545-3p. FAM98A was a direct target of miR-545-3p, and miR-545-3p hindered ECa cell progression via targeting FAM98A. Circ-IFT80 induced FAM98A expression through miR-545-3p. Furthermore, silence of circ-IFT80 suppressed tumor growth in vivo.Circ-IFT80 may promote the malignant progression of ECa cells at least in part by modulating miR-545-3p/FAM98A axis, providing a potential therapeutic target for ECa.Copyright © 2022. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.