Results: We demonstrated that Sprouty 4 (SPRY4) undergoes a dynamic palmitoylation cycle regulated by zinc finger DHHC-type palmitoyl transferase 7 (ZDHHC7) and PPT1, which modulates mitogen-activated protein kinase (MAPK) signaling and subsequently affects tumor cell proliferation, migration, apoptosis, and drug resistance. The gene discussed is SPRY4; the disease is neoplasm.