Taken together, the present study revealed a possible novel mechanism underlying malignant biological behavior caused by loss function of ZNF750 in OSCC in vivo or in vitro, and indicated that ZNF750 as a tumor suppressor plays a vital role in regulating transcriptional repressors and this function was related to depressed expression of E2F2 by ZNF750. Here, E2F2 is linked to neoplasm.