Antifouling surfaces are important in a broad range of applications. An effective approach to antifouling surfaces is to covalently attach antifouling polymer brushes. This work reports the synthesis of a new class of antifouling polymer brushes based on highly hydrophilic sulfoxide polymers by surface-initiated photoinduced electron/energy transfer-reversible addition-fragmentation chain transfer (PET-RAFT) polymerization. The sulfoxide polymer brushes are able to effectively reduce nonspecific adsorption of proteins and cells, demonstrating remarkable antifouling properties. Given the outstanding antifouling behavior of the sulfoxide polymers and versatility of surface-initiated PET-RAFT technology, this work presents a useful and general approach to engineering various material surfaces with antifouling properties, for potential biomedical applications in areas such as tissue engineering, medical implants, and regenerative medicine.