A crystalline silicon surface can be made biocompatible and chemically stable by a self-assembled biofilm of proteins, the hydrophobins (HFBs) purified from the fungus Pleurotus ostreatus. The protein-modified silicon surface shows an improvement in wettability and is suitable for immobilization of other proteins. Two different proteins were successfully immobilized on the HFBs-coated chips: the bovine serum albumin and an enzyme, a laccase, which retains its catalytic activity even when bound on the chip. Variable-angle spectroscopic ellipsometry (VASE), water contact angle (WCA), and fluorescence measurements demonstrated that the proposed approach in silicon surface bioactivation is a feasible strategy for the fabrication of a new class of hybrid devices.