Local and continuous release of nitric oxide (NO) has been suggested to be a potential and desirable demand for blood contacting implants. However, the life time of NO release from polymer films is limited by the reservoir of loaded NO donor. In situ generation of NO via catalytic decomposing the endogenous S-nitrosothiols (RSNOs) at the blood/material interface is a novel and challenging approach. Herein, a copper-incorporated film was constructed with the copolymerization of catechols (catechol or epigallocatechin gallate (EGCG)) and collagen. FT-IR results suggested the successful deposition of catechol/collagen copolymer film. The XPS results demonstrated the existence of copper on the surfaces. AFM results demonstrated that copper particles were formed in the thin polymeric film. Copper-incorporated samples presented a capability of generating physiological levels of NO. Difference of the generated amount of NO was associated with the Cu (I) concentration during the testing period, demonstrated by micro-BCA assay. NO-generating films not only significant properties on inhibiting platelet activation and adhesion, but also dramatically decreased smooth muscle cell adhesion. Such copper-incorporated film might suggest potential in the design of vascular devices.