Sugar-based trisiloxane surfactants (N-siloxanegluconamides and N-siloxanelactobionamides, denoted as Si(3)NGA and Si(3)NLA) with the amphiphilic structures were successfully prepared. Polyurethane (PU) was grafted with 2-carboxyethyl acrylate (CEA) by the means of UV-induced graft polymerization, and further introduction of the Si(3)NGA and Si(3)NLA by conjugating the amino groups and acid groups. The surface graft polymerization was confirmed by attenuated total reflection Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy, respectively. Water contact angle, protein adsorption, and platelet adhesion measurements were used to evaluate the hydrophilicity and hemocompatibility of the films. It was found that the Si(3)NGA-modified substrates obviously suppressed protein adsorption and platelet adhesion, while Si(3)NLA-modified substrates exhibited a higher protein adsorption and a coagulating performance of blood.