A disintegrin and metalloprotease 8 (ADAM8) is involved in the tumorigenesis of several types of solid tumors. However, its exact role in gastric cancer (GC) remains unclear. The aim of this study was to evaluate the clinical significance of ADAM8 in GC and to explore its biological effects on gastric carcinogenesis. In this study, quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemical staining analysis revealed that ADAM8 messenger RNA expression was significantly upregulated in GC tissues compared with noncancerous tissues (P = 0.004), and that positive ADAM8 expression is much more common in tumor tissues compared with normal tissues (P < 0.001) and is correlated with T stage (P = 0.036), N stage (P = 0.048), vessel invasion (P = 0.002), and a shorter patient overall survival (P = 0.024). In vitro assay indicated that ADAM8 overexpression promoted cell growth and increased migration and invasion abilities by decreasing the p-p38/p-extracellular regulated protein kinases (p-ERK) ratio. In conclusion, ADAM8 promotes GC cell proliferation and invasion, and its expression is positively correlated with poor survival, indicating that it might be a promising target in GC therapy.