To explore the prognostic related factors and mechanisms of gastric cancer (GC), we performed the systematic analysis with integrated bioinformatics tools based on multiple on-line datasets. With uni-variate COX analysis, we screened out 37 survival hazardous genes in GC. Further GO assays disclosed that the signatures related with extracellular matrix and structure, and the functions of "cell adhesion molecule binding" and "integrin binding" were the vital mechanisms of disease progression, and tissue inhibitor of metalloproteinase-2 (TIMP2) was the potential biomarker for prognosis. Based on GSEA, GSVA and GCN, TIMP2 was demonstrated to interact with multiple integrin pathways and involve in the regulation of EMT, cell adhesion, and angiogenesis of GC. The associations of TIMP2 expression with reduced OS and RFS of patients were declared by Kaplan-Meier analysis, and further confirmed by 1000 internal bootstrap replications and external KM plotter analysis. With multi-variate COX regression and time-dependent ROC analysis, we validated the prediction independency and capacity of TIMP2 for prognosis. The relationships of TIMP2 with clinicopathological characteristics were also uncovered. Taken together, our findings identify TIMP2 as the novel candidate biomarker for poorer outcome of GC patients, and revealed the underlying functions of TIMP2 and the potential mechanisms for GC progression.