Copolymerization of polydimethylsiloxane, polyurethane, and hydroxyethyl methacrylate (PDMS-PU-HEMA) hydrogel was performed. After treating with oxygen plasma, the sodium salt of 4-styrenesulfonic acid (NASS) was grafted onto the hydrogel in a one-step process. The surface density of peroxide active groups was determined by the iodide method. The hydrophilicity of the hydrogels surface was evaluated by measuring the water contact angle and water retention. The result demonstrated that oxygen plasma treatment and NASS grafting can improve the hydrophilicity. In addition, in order to evaluate cell compatibility, L929 fibroblasts cells were cultured on the surface of these hydrogels and the cell number was determined by the MTT testing. The results show that plasma treatment and NASS grafting can cause higher cell adhesion and cell growth rates than untreated PDMS-PU-HEMA. Furthermore, NASS grafting can also reduce the platelet adhesion and protein adsorption, hence effectively extending the blood coagulation times. Consequently hydrophilicity, cytocompatibility and hemocompatibility were greatly enhanced by the NASS grafting of PDMS-PU-HEMA.