Angiogenic activity in solid tumors has been demonstrated to promote metastasis through the activation of certain proteins involved in the epithelial-mesenchymal transition-associated process. The molecular mechanism underlying multiple myeloma-induced angiogenesis involves angiogenic cytokines by plasma cells as well as their induction within the microenvironment. Integrin-linked kinase (ILK) is a highly evolutionarily conserved intracellular protein that was originally identified as an integrin-interacting protein, and extensive genetic and biochemical studies have identified ILK expression to be vital during tumor-driven angiogenesis. In the present study, it was identified that angiogenic factors were upregulated in mesenchymal stem cells (MSCs) that were co-cultured with multiple myeloma cell lines. It was also revealed that upregulated ILK expression significantly promoted the capillary-formation ability of MSCs. The concentrations of angiogenic factors were significantly decreased compared with non-targeting siRNA-transfected and control MSCs. MSCs may participate in inducing the angiogenic response in multiple myeloma depending on ILK expression.