In this study, physicochemical and proteomic analyses were performed to investigate the effect of modified atmosphere packaging (MAP) on the quality of postharvest loose-leaf lettuce. The results showed that MAP enhanced the sensory characteristics of loose-leaf lettuce and delayed the incidence of postharvest deterioration by suppressing weight loss, electrolyte leakage, and reactive oxygen species levels. MAP-inhibited storage-induced programmed cell death may be attributed to a lower expression of protein disulfide isomerase and a higher expression of oligonucleotide/oligosaccharide binding fold nucleic acid binding site protein and reducing glutamine synthase levels. Also, we explore the potential of MAP to protect against oxidative damage in loose-leaf lettuce by potentially modulating the expression levels of NAC family proteins, which may enhance signaling and the expression of cytochrome c oxidase and membrane-bound pyrophosphate in the oxidative phosphorylation pathway. In addition, MAP potentially delayed postharvest senescence and extended the shelf life of lettuce by regulating key protein metabolic pathways that may reduce respiration rates. These include the NAC family of proteins, enzymes in the oxidative phosphorylation pathway, glutamine synthetize, and other crucial metabolic routes. These findings provide a scientific basis for enhancing the postharvest preservation of leafy vegetables, such as loose-leaf lettuce, through MAP technology.