This study performed quantitative lysine lactylation proteomic analysis on paired hepatocellular carcinoma (HCC) and adjacent normal tissues from one clinical patient using high-resolution mass spectrometry. We aimed to identify differentially lactylated proteins and explore their potential roles in HCC tumorigenesis and progression. The data provide a valuable resource for understanding the functional implications of lactylation in HCC and may facilitate the development of novel diagnostic or therapeutic targets.