Clinically, HMGB3 expression was positively correlated with TGIF2 and TGF-β, and patients with ESCC who positively co-expressed TGIF2/HMGB3, HMGB3/TGF-β, or TGIF2/TGF-β exhibited poor prognosis. This evidence concerns the gene HMGB3 and esophageal squamous cell carcinoma.