Background and objective Endometrial carcinoma (EC) is one of the most frequently diagnosed malignancies in females. Dysregulation of lncRNA TDRG1 has been widely documented in several cancers, including EC. However, the mechanism of this lncRNA involving in EC progression remains to be further elucidated. Materials and methods The enrichment levels of TDRG1 in EC tissues and cell lines were examined by RT-qPCR. Flow cytometry, cell counting kit-8 (CCK-8), transwell, and Western blot assays were conducted to assess whether TDRG1 knockdown could affect cell cycle arrest, proliferation, migration, invasion, and apoptosis of EC cells. The phosphorylation levels of mTOR, AKT and PI3K that associated with PI3K/Akt/mTOR pathway were determined by Western blot assay. Results TDRG1 expression was markedly upregulated in EC tissues and cell lines. Knockdown of TDRG1 significantly induced cell cycle arrest and apoptosis, inhibited cell proliferation, restrained the invasion and migration abilities in EC cells. Moreover, TDRG1 silencing decreased the protein levels of p-AKT, p-PI3K, and p-mTOR of EC cells. Conclusion Our data underlined the implication of TDRG1 in EC progression, proposing that targeting TDRG1 might be a potential therapeutic avenue in EC.