Through high‐throughput sequencing, we identified the key regulatory target of cisplatin‐induced OSCC metastasis, GSDMD, and elucidated that the regulation of OSCC metastasis by GSDMD does not depend on its classical pyroptosis pathway but rather on a new regulatory mechanism mediated by its interaction with MMP14, thereby inducing the tumor EMT and promoting metastasis. Here, MMP14 is linked to neoplasm.