The micro- or nano-structured mold used for polymer embossing typically must be coated with an anti-adhesion material to reduce its interaction with the embossing. The mold is typically made by nickel sulphamate electroforming. For the anti-adhesion coating to adhere to the mold, the nickel mold surface must be clean and preferably unoxidized or possess reactive groups suitable for covalent bonding with the anti-adhesion coating. The effectiveness of plasma cleaning using mixtures of oxygen (O-2) and tetrafluoromethane (CF4) with varying ratios versus liquid-only cleaning was investigated. To simulate the nickel mold, Ni200 alloy was used. Plasma treatment using mixtures of O-2 and CF4 was found to be more effective in cleaning the Ni200 surface than liquid-only cleaning or pure O-2 or pure CF4 plasma treatment. Using a 1:1 O-2/CF4 mixture plasma, the contact angles of water, glycerol and diiodomethane on Ni200 were the lowest and the calculated surface energy was the highest among the investigated treatments. From X-ray photoelectron spectroscopy (XPS), the amount of organic contamination on Ni200 was significantly reduced with plasma treatment. For liquid-only cleaned samples, metallic nickel, NiO and Ni(OH)(2) are present on the surface. With pure O-2 or pure CF4 or 1:1 O-2/CF4 mixture plasma, both oxidation and fluorination occur and the surface contains combinations of NiF2, Ni(OH)(2), Ni(OH)F, Ni2O3 and NiO1.5F instead (without metallic nickel and NiO). The proportions of these different compounds vary according to the O-2/CF4 ratio; O/Ni ratio is highest for pure O-2 plasma treatment, whilst F/Ni is highest for pure CF4 plasma treatment.