A disintegrin and metallopeptidase with thrombospondin motifs (ADAMTSs), which is frequently dysregulated in cancers and is involved in carcinogenesis and cancer progression. The present study identified that ADAMTS8 expression is downregulated in esophageal squamous cell carcinoma (ESCC) tissues when compared with nontumor tissue. The expression of ADAMTS8 is closely associated with clinical stage and lymph node metastasis in patients with ESCC. Furthermore, functional studies have shown thatADAMTS8overexpression could reduce abilities of proliferation, migration, and invasion and promote apoptosis of ESCC cells. Meanwhile, monocyte chemotactic protein-1 and interleukin-6 are markedly deregulated byADAMTS8overexpression. Consistently,in vivodata showed thatADAMTS8overexpression led to a reduction in tumor growth. These results indicate that alteringADAMTS8expression could modify the outcomes of ESCC by inhibiting cell proliferation and invasion, while promoting the apoptosis of ECSS cells. Thus,ADAMTS8represents a potential therapeutic target for ESCC therapy.