Abstract: To develop a new method for the sterilization of fresh-cut lettuce, plasma-activated water (PAW) combined with dielectric barrier discharge (DBD) plasma technology was applied in this study. Response surface methodological approach was performed to determine the optimal sterilization process parameters. Meanwhile, the microbial count, color, browning degree, firmness and weight loss rate were evaluated to investigate the effects of combined cold plasma treatments on the qualities of fresh-cut lettuce during the storage. Results showed that the total viable bacteria count on the surface of fresh-cut lettuce was (0.48±0.07) lg CFU/g under the optimal treatment conditions when PAW preparation time was 130 s, PAW soaking time was 5 min, and DBD plasma treatment time was 135 s. Moreover, during 7 days of storage, the combined cold plasma treatments could effectively inhibit the growth of microorganisms, maintain the color and firmness of fresh-cut lettuce, delay the increase of weight loss rate, and inhibit the occurrence of browning, which would effectively prolong the shelf life of fresh-cut lettuce.