Abstract: By taking novel fermented lettuce as the experimental material, the quality changes of samples in the high hydrostatic pressure (HHP) treatment group, pasteurization group, and untreated group during storage were compared. The results demonstrate that HHP treatment can effectively inhibit microbial reproduction, maintain product quality, and significantly extend shelf life. The initial total bacterial count is reduced to 2.09 lg(CFU/mL) after HHP treatment and remains below the safety limit of 6 lg(CFU/mL) throughout storage. The shelf life reaches 70 days at 4℃ and 30 days at 25℃, which is significantly longer than that of the pasteurization group (50 days at 4℃ and 20 days at 25℃) and the untreated group (bag swelling within 5 days). Furthermore, HHP treatment better preserves the hardness, chewiness, and bright green color of the fermented lettuce, while maintaining nitrite content at a consistently low level of 0.02–0.06 mg/kg. This value is far below the national food safety standard (GB2762—2022) limit of 20 mg/kg, representing only approximately 0.1%–0.3% of the permitted threshold. This study provides technical support for the green and efficient processing as well as safe preservation of fermented lettuce.