Background Esophageal squamous cell carcinoma (ESCC) is the most prevalent histological subtype of esophageal cancer. miR-139-5p has been shown to have abnormal expression in ESCC. We intend to probe into the roles of miR-139-5p in ESCC, thus providing references for investigating underlying therapeutic targets.Methods miR-139-5p expression in esophageal carcinoma was predicted by the Starbase online website. miR-139-5p expression in human ESCC cell lines (KYSE-150, KYSE-410, KSE-30) and human esophageal epithelial cell line Het1A was determined by reverse transcription quantitative polymerase chain reaction (RT-qPCR). KYSE-150 cells were manipulated with miR-139-5p mimic to upregulate miR-139-5p. Cell colony formation, viability, apoptosis, migration, and invasion were assessed by colony formation assay, CCK-8, flow cytometry, wound healing test, and Transwell. The targeted binding between miR-139-5p and TGIF1 was predicted on Starbase, Targetscan, and miRDB online websites and verified by Dual-Luciferase assay. Cells were transfected with miR-139-5p mimic and pcDNA3.1 TGIF1. The phosphorylation levels of TGF beta pathway-related proteins Smad2 and Smad3 were assessed by RT-qPCR and western blot.Results miR-139-5p was underexpressed in ESCC cells. miR-139-5p overexpression reduced ESCC cell viability, migration, and invasion, and promoted apoptosis. TGIF1 overexpression averted miR-139-5p mimic-inhibited ESCC cell growth. miR-139-5p overexpression decreased the phosphorylation levels of TGF beta pathway-related proteins Smad2 and Smad3, while the phosphorylation levels were increased by additional TGIF1 vector transfection.Conclusion miR-139-5p mediates TGIF1 to regulate TGF beta pathway and inhibit ESCC cell growth.