To enhance the interfacial adhesion between poly(tetrafluoroethylene-co-hexafluoropropylene) (FEP) film and functional coatings, such as silver (Ag) coating, among others, the surface activation of FEP film has to be performed. Among various activation strategies, chemical activation, such as using naphthalene sodium system, is one of the most efficient methods. However, the effect of chemical activation on the interface interaction between the activated FEP and functional coating is rarely investigated. Herein, the FEP film was activated by naphthalene sodium solution under different conditions, and then the Ag layer was coated onto its surface by vacuum Ag deposition. Based on experimental results and density function theory (DFT) calculation, it is indicated that oxygen-containing functional groups (such as C=O and C-OH groups), introduced onto the surface of FEP by the chemical activation, play a key role in boosting the interface interaction, which is due to the strong interaction between the oxygen-containing functional groups and Ag atoms. In addition, the concentration of naphthalene sodium solution, activation time, and winding speed of Ag- deposition can have a significant impact on the microstructures of Ag coating and the interfacial adhesion between the activated FEP and Ag coating. Under the conditions of high concentration (0.9 M), medium activation time (15 min), and high winding speed (0.8 m min-1), there is the best interface adhesion.