Hyaluronic acid (HA) has been known one of the abundant components of the extracellular matrix in tumor tissue. HA affects both tumor cells and stromal cells and contributes tumor malignancy. Most of the studies have addressed the effects of hyaluronic acid as modulator in tumor microenvironment on behavior of tumor cells. On the other hand, crosstalk between overly accumulated HA and immune cells is not clearly determined. Therefore, in this study, I construct a HA based three-dimensional (3D) matrix and examine the effects of HA on characteristics of immune cells in gene and protein level. Through this research, it can contribute to in-depth understanding of behavior of immune cells in microenvironmental view.