We demonstrated that melatonin inhibits migration of HSC-3 and OECM-1 oral cancer cells, inhibits the gene expression and enzyme activity of MMP-9, inhibits phosphorylation of ERK1/2, inhibits the expression of CREBBP and EP300 transcription factors, and reduces histone acetylation on the MMP-9 gene. Here, EP300 is linked to lip and oral cavity carcinoma.