Abstract: Objective To investigate the expression of human A disintegrin and metalloproteinase with thrombospondin motif 18(ADAMTS18)in human hepatocellular carcinoma(HCC)and its impact on migration and invasion of HCC cells. Methods The expression of ADAMTS18 in 50 paired HCC and matched tumor adjacent tissues were detected by immunohistochemistry. The relationship between ADAMTS18 expression and clinical features was analyzed. ADAMTS18 was up-regulated in Huh-7 cells by overexpression of plasmids. The impacts of overexpression of ADAMTS18 on Huh-7 cell migration and invasion, phosphorylated AKT and expression of E-cadherin in Huh-7 cells were explored by Transwell chamber assays, Western blot assays, respectively. Results The expression of ADAMTS18 was decreased in HCC tissues(P=0.003). Low expression of ADAMTS18 was associated with vascular infiltration(P=0.018)and TNM staging(P=0.038). Overexpression of ADAMTS18 inhibited migration of Huh-7 cells(P=0.038), invasion(P=0.027), and AKT - phosphorylation(P=0.047), but increased E-cadherin expression(P=0.032). Conclusion Lower expression of ADAMTS18 is closely associated with features of HCC malignancy, ADAMTS18 in HCC tissues may suppress cell migration and invasion through inhibiting AKT phosphorylation.