This study was designed to develop a cold plasma +222 nm ultraviolet (CP + UV) sterilization device in the food industry. Response surface methodology was applied to evaluate the effects of three treatment conditions on the antibacterial activity of CP + UV. The optimum treatment conditions (plasma gas flow: 4 m3/min, irradiation distance: 4 cm, treatment time: 60 s) were selected to optimize the reactor parameters of CP and 222 nm UV sterilization equipment, and its effects against the growth of S. aureus on different food contact materials were investigated. Results showed that the antibacterial activity against S. aureus was strongest when the plasma was operated at 8.5 kHz, 2.5 W/cm2 with two net layers of electrodes arranged transversely at a distance of 5 cm between the plasma outlet plane and UV centerline plane. After 60 s of CP + UV treatment, the number of S. aureus on the glass sheet, polypropylene film, corrugated paper, and kraft paper decreased by 4.5, 4.1, 1.5, and 2.4, respectively (p < 0.05). In summary, a novel CP + UV device was developed, which can be used for sterilization on different food surfaces, which potentially contributes to the development of the food industries. •Combination of CP and UV treatment was used for sterilization.•Staphylococcus aureus on the glass sheet decreased by 5.40 Log CFU/cm2 after 60s treatment.•The order of sterilization was glass sheet > OPP film > kraft paper > corrugated paper.•A novel CP + UV device was developed to sterilize different food surfaces.