The authors' previous study demonstrated that Golgi phosphoprotein 3 (GOLPH3) was significantly overexpressed in esophageal squamous cell carcinoma (ESCC), correlating with poor patient survival. In the present study, GOLPH3 stable overexpression and knockdown KYSE-140 cell lines were constructed. Cell proliferation, colony formation, cell cycle progression and tumorigenesis assays were performed. The results revealed that GOLPH3 promoted ESCC cell growth and proliferation. The effects of GOLPH3 on the mechanistic target of rapamycin (mTOR) and Wnt/beta-catenin signaling pathways were investigated using western blot analyis and dual-luciferase reporter assays, and were observed to be activated in cells with GOLPH3 overexpression. Furthermore, overexpression of GOLPH3 resulted in the downregulation of p21 protein, upregulation of cyclin D1 and increased retinoblastoma-associated protein phosphorylation, consequently leading to accelerated cell cycle progression. In addition, GOLPH3 knockdown resulted in reversed effects. The results of the current study suggest that GOLPH3 serves an important role in promoting tumorigenicity of ESCC via mTOR and Wnt/beta-catenin signaling pathway activation.