Abstract: The present invention relates to a hydrophilic surface structure of the non-hydrophilic substrate and the manufacturing method for using the same. The hydrophilic substrate surface structure is fabricated by forming an amphiphilic polymer layer, a cross-linked stacking layer, and a hydrophilic layer in sequence on the surface of a non-hydrophilic substrate. For example, the hydrophobic surface of poly(dimethylsiloxane) (PDMS) can be made from hydrophobic to hydrophilic and the hydrophilicity can be retained for a long period of time and resist protein adsorption. The hydrophilic thin films give long term stability to the PDMS surface by resisting hydrophobicity recovery, which is the major problem with PDMS. The disclosed method can further be used in the immobilization of protein and other molecules. This method can also be used for modifying other substrates which suffer problems of surface instability.