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The utilization of improper thawing methods can potentially compromise the quality of food, while the degeneration of myofibrillar protein during the thawing process directly impacts the alteration of physical and chemical properties of food. The effects of high-pressure thawing (HPT), water immersion thawing (WIT), and air thawing (AT) on the quality and myofibrillar protein (MP) denaturation of salmon were investigated. The thawing times of WIT, AT, and HPT-300 MPa were 23.6,116.6, and 10.1 min, respectively, suggesting that HPT improved the rate of thawing. Compared with conventional thawing methods, the color difference of HPT-100 MPa and the water loss of HPT-150 MPa were reduced by 56.77% and 6.77%, respectively, and textural deterioration was weakened, preserving the quality of thawed salmon. In the current study, 200 and 300 MPa were the pressure thresholds for the degradation of salmon myosin and actin proteins, respectively. Meanwhile, HPT induced noticeable changes in the stability, secondary structure, and micromorphology of salmon MPs, which affected various physical and chemical properties of thawed salmon samples, such as water loss, color, and texture. In particular, the spatial structure stability of MP can be better maintained at HPT-100 MPa and HPT-150 MPa. HPT can be an alternative strategy to the traditional thawing of salmon.