Endometrial cancer (EC) is one of the most common gynecological cancer types worldwide. However, to the best of our knowledge, its underlying mechanisms remain unknown. The current study downloaded three mRNA and microRNA (miRNA) datasets of EC and normal tissue samples, GSE17025, GSE63678 and GSE35794, from the Gene Expression Omnibus to identify differentially expressed genes (DEGs) and miRNAs (DEMs) in EC tumor tissues. The DEGs and DEMs were then validated using data from The Cancer Genome Atlas and subjected to gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis. STRING and Cytoscape were used to construct a protein-protein interaction network and the prognostic effects of the hub genes were analyzed. Finally, miRecords was used to predict DEM targets and an miRNA-gene network was constructed. A total of 160 DEGs were identified, of which 51 genes were highly expressed and 100 DEGs were discovered from the PPI network. Three overlapping genes between the DEGs and the DEM targets, BIRC5, CENPF and HJURP, were associated with significantly worse overall survival of patients with EC. A number of DEGs were enriched in cell cycle, human T-lymphotropic virus infection and cancer-associated pathways. A total of 20 DEMs and 29 miRNA gene pairs were identified. In conclusion, the identified DEGs, DEMs and pathways in EC may provide new insights into understanding the underlying molecular mechanisms that facilitate EC tumorigenesis and progression.