Here, we investigated the mechanism of PRC2 inhibitors in B‐cell lymphoma using a whole‐genome CRISPR/Cas9 knockout (KO) screen and identified the Bone Morphogenetic Protein (BMP)‐Activin A Receptor Type 1 (ACVR1) signaling pathway is critical for the anti‐tumor efficacy of PRC2 inhibitors. This evidence concerns the gene ACVR1 and neoplasm.