This dataset contains quantitative proteomics and acetylproteomics data from HL-1 cardiomyocytes subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) with or without phillyrin treatment. The aim was to identify differentially expressed proteins and acetylated peptides involved in the cardioprotective effect of phillyrin, using label-free mass spectrometry on an Orbitrap Astral instrument.