Poly(dimethylsiloxane) (PDMS) has been widely used in the field of microfluidics, optical systems, and sensors. However, the hydrophobic nature of PDMS leads to low surface wettability and biofouling problems due to the nonspecific proteins-hydrophobic surface interactions and cell/bacterial adhesion. In this work, the PDMS surface was first introduced with amino groups (PDMS-NH2) via KOH-catalyzed reaction with 3-aminopropyltriethoxysilane (APTES). The PDMS-NH2 was then grafted with poly(N-vinylpyrrolidone) (PVP) based on the self-adhesion reaction between the amino surface and catechol-functionalized PVP (CA-PLL-PVP). CA-PLL-PVP as a comb-polymer was synthesized by conjugating PVP-COOH along with caffeic acid to the epsilon-polylysine backbone. A significantly enhanced water wettability was observed with contact angles dropped from 116 degrees to 14 degrees after coating with CA-PLL-PVP. The coated surface demonstrated excellent antifouling performance that no appreciableStaphylococcus epidermidisbiofilm formation could be observed. This novel facile antifouling coating on PDMS surface may find greater biomedical applications to eliminate the potential adherence problems caused by natural biofouling.