Background <p>Esophageal squamous cell carcinoma (ESCC) is a prevalent and aggressive malignancy. While microRNAs (miRNAs) are known to play a critical regulatory role in the occurrence and progression of ESCC, the underlying mechanisms remain incompletely understood. Therefore, the aim of this study was to investigate the effect of miR-196a-5p on the proliferation, migration, and invasion of ESCC and its mechanism.</p> Methods <p>The role of miR-196a-5p in the progression of ESCC was explored with CCK8, colony formation, and Transwell assays, and Western blot analysis was used to detect epithelial–mesenchymal transition (EMT). The regulatory effect of miR-196a-5p on ESCC was further verified through a xenograft experiment on nude mice.</p> Results <p>miR-196a-5p was significantly upregulated in ESCC, and the overexpression of miR-196a-5p considerably promoted the proliferation, migration, and invasion of ESCC cells in vitro. The expression level of E-cadherin decreased, while N-cadherin and vimentin increased, indicating that the EMT of ESCC cells was promoted. Conversely, miR-196a-5p downregulation had the opposite effects. In vivo experiments confirmed that miR-196a-5p overexpression promoted ESCC proliferation and EMT. Furthermore, we identified leukemia inhibitory factor receptor (LIFR) as a target gene of miR-196a-5p in ESCC and was negatively regulated by miR-196a-5p. LIFR overexpression can rescue the ability of miR-196a-5p to promote ESCC cell proliferation and invasion, and offset the cell migration and EMT caused by miR-196a-5p.</p> Conclusions <p>miR-196a-5p promotes the proliferation, migration, and invasion of ESCC by targeting LIFR and regulating the EMT, highlighting its potential as a diagnostic biomarker and therapeutic target.</p>