Gastric cancer (GC) is one of the most common cancers and the second leading cause of cancer deaths in the world. Many factors have been reported regarding the progression and development of GC. In this study, we aimed to investigate the correlation of 3-phosphoinositide dependent protein kinase-1 (PDK-1) with cell viability, migration, and invasion of GC. The expression of PDK-1 was measured in different GC cell lines. Thereafter, the expression of PDK-1 was interfered by small hairpin RNA (shRNA) and then incubated with or without the inhibitor of nuclear factor-κB (NF-κB) pyrrolidine dithiocarbamate (PDTC). We then investigated the effects of PDK-1 aberrant expression on GC cell viability, migration, invasion, and the epithelial-mesenchymal transition (EMT) progress. The results showed that PDK-1 was highly expressed in GC cells, and PDK-1 promoted cell viability, migration, invasion, and EMT in GC. Moreover, we confirmed that PDK-1 activated the phosphatidylinositol 3-hydroxy kinase (PI3K)/AKT and NF-κB signaling pathways. However, administration of PDTC reversed the effects of overexpression of PDK-1 on cell migration and invasion. All these findings suggest that PDK-1 may be involved in progression of GC and could be a new therapeutic target for this disease.