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The transcription factor signal transducer and activator of transcription 3 (STAT3) contributes to cell proliferation, apoptosis and motility in human cancer cells. We aim to elucidate the function of STAT3 in esophageal carcinogenesis process and molecular mechanisms. We showed that hyperactivated STAT3 in esophageal carcinogenesis tissues correlated with the overexpression of octamer transcription factor-1 (Oct-1). High STAT3 phosphorylation correlated with shorter survival compared with low STAT3 phosphorylation. STAT3 and Oct-1 expression levels affected the proliferation and colony formation of Eca-109 esophageal squamous cell carcinoma cells by altering Erk and Akt activation. Nevertheless, STAT3 regulated the migration and invasion of esophageal squamous cell carcinoma cells independent of Oct-1. In conjunction with Oct-1, STAT3 inhibited apoptosis in esophageal squamous cell carcinoma cells. Constitutively activated STAT3 in normal human esophageal epithelium cells (HET-1A) elevated Oct-1 expression,and promoted proliferation and decreased apoptosis. STAT3 activated HET-1A cells to form tumors in vivo, suggesting that overactivated STAT3 is sufficient for carcinogenesis. We further confirmed the colocalization of STAT3 and Oct-1 in the nucleus and found that STAT3 regulates the transcription and expression of Oct-1 by directly targeting its promoter. Activated STAT3 also upregulated many genes associated with Oct-1. Together, our results indicate that STAT3 plays a crucial role in esophageal carcinogenesis by regulating the cell proliferation and apoptosis in conjunction with Oct-1. [ABSTRACT FROM AUTHOR]