Our CRISPR screening also revealed that multiple members of TrxG proteins including KMT2A, KMT2D, SETD1A, SMARCE1, and SMARCD1 and PcG proteins including CBX4 and PCGF5 orchestrate HCC stemness, suggesting that TrxG and PcG proteins might cooperate or crosstalk to promote HCC stemness. Here, SMARCE1 is linked to hepatocellular carcinoma.