Alaska pollock is an important protein source which is extensively used in the food industry. Pollock protein isolates (PPI) with significantly enriched protein contents could be prepared using isoelectric solubilization/precipitation (ISP) processing; however, the functional properties of this process is limited by the large amount of water-insoluble proteins. In this study, we investigated the influence of high hydrostatic pressure (HHP) treatment on the solubility and structural changes of PPI. PPI obtained using ISP is treated with hydrostatic pressures of 200, 300, 400, and 500 MPa for up to 15 min, and the HHP-treated samples were observed to exhibit significantly improved solubilities. Further biochemical assays reveal that the continuous HHP treatments reduce the contents of free sulfhydryl groups and promote the formation of macromolecules with better water solubilities, which may induce the solubility improvements of the HHP-treated PPI. Our results indicate that HHP can be utilized to effectively prepare highly water-soluble Alaska pollock protein in food processing.