By analyzing the differential expression of SUMOylation regulators in OSCC between tumor tissues and normal tissues, we found that the 11 genes including PIAS3, RANBP2, USPL1, SENP6, SENP2, SENP5, SAE1, UBA2, PIAS4, UBE2I, and SENP3 were highly expressed. The gene discussed is PIAS4; the disease is neoplasm.