For investigating the effects of high pressure in combination with thermal (HP-T) treatment on lipid hydrolysis and oxidation in pork, minced pork was treated with combinations of different pressures (200, 400, and 600 MPa) and temperatures (20 and 50 °C); the content and fatty acid profiles of intramuscular lipids, peroxide value (POV), thiobarbituric acid reactive substances (TBARS), and lipoxygenase (LOX) activity were measured. Treatment of samples at pressures of 400 MPa or above significantly enhanced the uneven hydrolysis of phospholipids, resulting in more polyunsaturated fatty acids (PUFA) in degraded phospholipids or generated free fatty acids (FFA); treatment temperature had a synergistic effect on phospholipid hydrolysis. Both POV and TBARS values increased with the intensity of treatment conditions until they reached the highest value, and then gradually decreased; neither corresponded closely with the changes in LOX activity. ANOVA-partial least squares regression (APLSR) analysis indicated that phospholipid hydrolysis positively correlated with TBARS but weakly correlated with POV. Thus, phospholipid hydrolysis could enhance lipid secondary oxidation, which mainly arising from auto-oxidation.