In this section, a detailed summary of our current knowledge about the modulatory effects of PTMs on non-histone proteins (Table 1) and histone proteins (Table 2) and their roles in regulating cancer stemness in the five most common types of GI cancers, including hepatocellular carcinoma (HCC), esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), and pancreatic cancer (PC), will be reviewed. Here, H2BC12L is linked to hepatocellular carcinoma.