Our findings demonstrate that ZMYND11 exerts a dual tumor-suppressive role: first, by inhibiting HNRNPA1-mediated stress granule formation, ZMYND11 promotes apoptosis in cancer cells under stress; second, ZMYND11 suppresses aerobic glycolysis by inhibiting HNRNPA1-driven alternative splicing of PKM2. This evidence concerns the gene PKM and cancer.