A hybrid polymer brush containing poly(ethylene glycol) (PEG) chains and polyhedral oligosilsesquioxane (POSS) on a gold surface is presented that exhibits an excellent protein resistance and long-term stability. A series of hybrid polymer brushes with different length and numbers of PEG chains are fabricated through chemisorption of PEG-POSS-SH on the gold surface. Protein adsorption of these hybrid brushes is investigated. The amount of protein adsorption decreases with increasing lengths and numbers of PEG chains. After immersion in BSA solution for two months, the PPS4 brushes retain their protein resistance, while a PEG-SH layer loses its non-fouling performance. These POSS-containing hybrid polymer brushes might offer an alternative for modification of gold surface with an excellent protein resistance for long-term applications.