Mesenchymal stem cells (MSCs) therapy has limitations due to the poor viability of MSCs after cell transplantation. Integrin-mediated adhesion is a prerequisite for cell survival, and also a key factor for the differentiation of MSCs. As a novel anti-death strategy to improve cell survival in the infarcted heart, MSCs were genetically modified to over-express integrin-linked kinase (ILK). The survival rate of ILK-transfected MSCs (ILK-MSCs) was augmented by about 1.5-fold and the phosphorylation of ERK1/2 and Akt in ILK-MSCs were increased by about 3- and 2-fold, respectively. ILK-MSCs resulted in increase of 2-fold in ratio of Bcl-2/Bax and inhibited caspase-3 activation, compared with hypoxic MSCs. Adhesion rate of ILK-MSCs also had a 30.0% increase on the cardiac fibroblast-derived 3D matrix and ILK-MSCs showed higher retention by about 4-fold than MSCs in infarcted myocardium. In vivo, ILK-MSC transplanted rats had a 12.0% smaller infarct size than MSC-treated rats after ligation of left anterior descending coronary artery. Transplantation of ILK-MSCs not only led to a 15.5% decrease in the fibrotic heart area, but also significantly reduced the apoptotic positive index by about 17.0% compared with ligation only. The mean microvessel count per filed in the infarcted myocardium of ILK-MSCs group (129.1짹23.5) was increased relative to sham group (19.3짹15.2) and MSCs group (68.9짹19.4). In conclusion, ILK gene further assisted cell survival, proliferation and adhesion, and improved myocardial damage compared to MSC only after transplantation.